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Integrin Structure
Published by Anonymous on 2007/9/27 (600 reads)
1: Crit Rev Immunol. 2006;26(5):391-406.


Structure and function of cas-L and integrin-mediated signaling.

Seo S, Ichikawa M, Kurokawa M.

Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Cas-L (Crk-associated substrate lymphocyte type), also known as HEF1 (human enhancer of filamentation 1) or NEDD9 (neural precursor cell-expressed, developmentally downregulated gene 9), is an adapter protein at focal adhesions and transmits various signals, mainly induced by integrins. Cas-L is a member of the Cas family proteins and is expressed preferentially in lymphocytes and epithelial cells. A number of previous studies have suggested that Cas-L plays an important role in lymphocyte movement and cell cycle. Recently, we reported a novel function of Cas-L in the immune system using gene-targeted mice. The Cas-L-deficient lymphocytes showed insufficient chemotactic response and perturbed cell adhesion. Moreover, a deficit of marginal zone (MZ) B cells was detected in the mutant mice. Here, we review the structure of Cas-L and several signaling pathways in which Cas-L is involved, based on the previous in vitro studies. Subsequently, biological functions of Cas-L and the relevance of Cas-L to human diseases are discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 17341185 [PubMed - indexed for MEDLINE]

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2: Cardiovasc Hematol Agents Med Chem. 2007 Jan;5(1):29-42.


Structure-activity relationship studies on ADAM protein-integrin interactions.

Lu X, Lu D, Scully MF, Kakkar VV.

Thrombosis Research Institute, Manresa Road, London, SW3 6LR, UK. xlu@tri-london.ac.uk

The ADAM (a disintegrin and metalloprotease) family of proteins possess multi-domain structures composed of a signal peptide, a prodomain, a metalloprotease domain, a disintegrin-like domain, a cysteine rich domain, an epidermal growth factor-like domain, a transmembrane domain and cytoplasmic tail. The disintegrin-like domain shares sequence similarity with the soluble venom disintegrins, a family of proteins which are potent inhibitors of integrin-mediated platelet aggregation and cell adhesion. Several ADAMs have been reported to interact with integrins, and the disintegrin-like domain may be crucial part in this respect. A description of structure-activity relationship of ADAM proteins interacting with integrin is outlined in this review. The review highlights recent reports on potential integrin family for ADAMs and how ADAMs selectively modulate interaction for integrin mediated cell function. Lastly, it describes progress in understanding the structural features and functional roles of the ADAMs in normal and pathological conditions and how this insight may assist the development of new therapeutic approaches.

Publication Types:
Review

PMID: 17266546 [PubMed - indexed for MEDLINE]

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3: Adv Immunol. 2006;91:111-57.


Targeting integrin structure and function in disease.

Staunton DE, Lupher ML, Liddington R, Gallatin WM.

ICOS Corporation, Bothell, Washington, USA. destaunton@comcast.com

Initially linked to the pathogenesis of inflammatory and hematologic diseases, integrins have become validated drug targets with the approval of five drugs. Moreover, there are several promising drug candidates in preclinical and clinical stages of development for multiple clinical indications. Integrins are attractive drug targets as their antagonism can block several steps in disease progression or maintenance. Integrin inhibitors can block the proliferation, migration, or tissue localization of inflammatory, angiogenic, and tumor cells, as well as signaling and gene expression contributing to disease. There has been a rapid increase in the elucidation of integrin structure, their allosteric mechanisms of bidirectional signaling, and the structure of complexes with drugs. This information brings greater focus to how integrins support various cellular functions and how they have been and may be targeted to develop novel drugs. Here we review conformational switches, including an internal ligand, which allosterically regulate the transition from low- to high-affinity ligand binding. We address some of the successes, disappointments, and challenges in targeting competitive or allosteric sites to develop therapeutics. We also discuss new opportunities, including a structure-based approach to discover novel drugs to treat inflammatory and other diseases. This approach targets structural relatives of the von Willebrand factor A-domain present in integrins and many functionally diverse proteins.

Publication Types:
Review

PMID: 16938539 [PubMed - indexed for MEDLINE]

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4: J Clin Invest. 2005 Dec;115(12):3363-9.


Structure and function of the platelet integrin alphaIIbbeta3.

Bennett JS.

Hematology-Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6058, USA. bennetts@mail.med.upenn.edu

The platelet integrin alpha(IIb)beta(3) is required for platelet aggregation. Like other integrins, alpha(IIb)beta(3) resides on cell surfaces in an equilibrium between inactive and active conformations. Recent experiments suggest that the shift between these conformations involves a global reorganization of the alpha(IIb)beta(3) molecule and disruption of constraints imposed by the heteromeric association of the alpha(IIb) and beta(3) transmembrane and cytoplasmic domains. The biochemical, biophysical, and ultrastructural results that support this conclusion are discussed in this Review.

Publication Types:
Review

PMID: 16322781 [PubMed - indexed for MEDLINE]

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5: Annu Rev Cell Dev Biol. 2005;21:381-410.


Integrin structure, allostery, and bidirectional signaling.

Arnaout MA, Mahalingam B, Xiong JP.

Structural Biology Program, Leukocyte Biology and Inflammation Program, Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachussetts 02129, USA. arnaout@receptor.mgh.harvard.edu

Alphabeta heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin alphaVbeta3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.

Publication Types:
Research Support, N.I.H., Extramural
Review

PMID: 16212500 [PubMed - indexed for MEDLINE]

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6: Trends Biochem Sci. 2003 Jun;28(6):313-20.


Integrin structure: heady advances in ligand binding, but activation still makes the knees wobble.

Humphries MJ, McEwan PA, Barton SJ, Buckley PA, Bella J, Mould AP.

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, 2.205 Stopford Building, Oxford Road, Manchester, UK M13 9PT. martin.humphries@man.ac.uk

Integrins are one of the major families of cell-adhesion receptors. In the past year, the first structure of an integrin has been published, ligand-binding pockets have been defined, and mechanisms of receptor priming and activation elucidated. Like all major advances, however, these studies have raised more questions than they have answered about issues such as the mechanisms underlying ligand-binding specificity and long-range conformational regulation.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12826403 [PubMed - indexed for MEDLINE]

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7: Immunol Rev. 2002 Aug;186:125-40.


Erratum in:
Immunol Rev. 2003 Jun;193:146.

Integrin structure: new twists and turns in dynamic cell adhesion.

Arnaout MA.

Renal Unit, Leukocyte Biology & Inflammation Program, Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. arnaout@receptor.mgh.harvard.edu

The divalent-cation-dependent binding of alphabeta heterodimeric integrins to their ligands regulates most cellular processes. Integrin-ligand interactions are tightly controlled by inside-out activation signals. Ligand-bound integrins in turn transduce outside-in signals typical of other receptors. Precise information of how ligands bind to integrins is restricted to that of a small vWF A-type domain present in some alpha-subunits (alphaA). Both inside-out and outside-in signals elicit tertiary and quaternary changes in integrins, but the precise nature and scope and of these changes are unknown. The recently solved structures of the extracellular segment of integrin alphaVbeta3 in its unliganded and liganded states are generating exciting new insights into the design, wiring, function and regulation of this protein family. The structures reveal a surprising degree of flexibility at defined regions in the structure that is potentially controlled by cations. The quaternary structure of the ligand-binding region bears a striking resemblance to the nucleotide-binding pocket of G-proteins, implying analogous activation and signaling mechanisms. Structural links exist through which ligand-induced tertiary changes may be translated into quaternary changes and vice versa. The structures also raise the tantalizing hypothesis that alphaA is a regulated endogenous integrin ligand, so that no special regulatory features are needed in this integrin. These findings provide the framework for new investigations of structure-activity relationships in integrins, with important implications for targeting these receptors therapeutically [corrected].

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12234368 [PubMed - indexed for MEDLINE]

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8: Arthritis Res. 2002;4 Suppl 3:S69-78. Epub 2002 May 9.


Insights into integrin-ligand binding and activation from the first crystal structure.

Humphries MJ.

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, UK. martin.humphries@man.ac.uk

Integrin receptors transduce bidirectional signals between extracellular adhesion molecules and intracellular cytoskeletal and signalling molecules. The structural basis of integrin signalling is unknown, but the recent publication of the first crystal structure of the extracellular domain of integrin alphaVbeta3 has provided a number of insights. In this review, previous structure-function analyses of integrins that have employed biochemical and molecular biological approaches are placed in the context of the crystal structure, and novel routes to the development of integrin antagonists are discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12110125 [PubMed - indexed for MEDLINE]

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9: Annu Rev Biophys Biomol Struct. 2002;31:485-516. Epub 2001 Oct 25.


Conformational regulation of integrin structure and function.

Shimaoka M, Takagi J, Springer TA.

The Center for Blood Research, Department of Pathology and Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

Integrins are a structurally elaborate family of heterodimers that mediate divalent cation-dependent cell adhesion in a wide range of biological contexts. The inserted (I) domain binds ligand in the subset of integrins in which it is present. Its structure has been determined in two alternative conformations, termed open and closed. In striking similarity to signaling G proteins, rearrangement of a Mg(2+)-binding site is linked to large conformational movements in distant backbone regions. Mutations have been used to stabilize either the closed or open structures. These show that the snapshots of the open conformation seen only in the presence of a ligand or a ligand mimetic represent a high-affinity, ligand-binding conformation, whereas those of the closed conformation correspond to a low-affinity conformation. The C-terminal alpha-helix moves 10 A down the side of the domain in the open conformation. Locking in the conformation of the preceding loop is sufficient to increase affinity for ligand 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to conformational movements in other domains. The transition from the closed to open conformation has been implicated in fast (<1 s) regulation of integrin affinity in response to activation signals from inside the cell. Recent integrin structures and functional studies reveal interactions between beta-propeller, I, and I-like domains in the headpiece, and a critical role for integrin EGF domains in the stalk region. These studies suggest that the headpiece of the integrin faces down toward the membrane in the inactive conformation and extends upward in a "switchblade"-like opening motion upon activation. These long-range structural rearrangements of the entire integrin molecule involving multiple interdomain contacts appear closely linked to conformational changes in the I domain, which result in increased affinity and competence for ligand binding.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 11988479 [PubMed - indexed for MEDLINE]

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10: Int J Hematol. 2001 Dec;74(4):382-9.


Platelet integrin alphaIIbbeta3-ligand interactions: what can we learn from the structure?

Kamata T, Takada Y.

Department of Anatomy, Keio University School of Medicine, Tokyo, Japan. kamata@sc.itc.keio.ac.jp

Upon vascular injury, platelets initiate interaction with exposed subendothelial matrices through various receptors such as glycoprotein (GP) Ib/IX/V complex, alpha2beta1 integrin, and GPVI/FcRgamma. Although these interactions cannot sustain stable platelet thrombus formation by themselves, they ultimately lead to the activation of alphaIIbbeta3 integrin (GPIIb-IIIa complex [GPIIb-IIIa]), the most abundant receptor in platelets. The alphaIIbbeta3 integrin plays a central role in primary hemostasis by serving as a receptor for fibrinogen and von Willebrand factor (vWf). It establishes a stable interaction with vWf bound to the extracellular matrices and uses fibrinogen as a bridging molecule in platelet aggregate formation. The alphaIIbbeta3 integrin also plays an important role in the pathogenesis of thrombosis. Over the past decades, a tremendous amount of effort has been made to elucidate the ligand-binding mechanisms of alphaIIbbeta3, in part because of its clinical significance. Most of the studies have relied on biochemical analyses of purified alphaIIbbeta3 or recombinant proteins generated in vitro. With the lack of actual 3-dimensional structure, molecular modeling has provided a useful framework for interpreting such experimental data on structure-function correlation of integrin molecules. However, it has also generated disagreement between different models. The aim of this minireview is to summarize the past efforts as well as the recent accomplishments in elucidating the structure/function of alphaIIbbeta3. Finally, we will try to explain all those experimental data using the recently published crystal structure of the extracellular domains of the alphaVbeta3 heterodimeric complex.

Publication Types:
Review

PMID: 11794692 [PubMed - indexed for MEDLINE]

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11: Biochem Soc Trans. 2000;28(4):311-39.


Integrin structure.

Humphries MJ.

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, U.K. martin.humphries@man.ac.uk

The integrins are a family of alpha,beta heterodimeric receptors that mediate dynamic linkages between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are expressed by all multicellular animals, but their diversity varies widely among species; for example, in mammals, 19 alpha and 8 beta subunit genes encode polypeptides that combine to form 25 different receptors, whereas the Drosophila and Caenorhabditis genomes encode only five and two integrin alpha subunits respectively. Thousands of studies over the last two decades have investigated the molecular, cellular and organismal basis of integrin function. Gene deletion has demonstrated essential roles for almost all integrins, with the defects suggesting widespread contributions to both the maintenance of tissue integrity and the promotion of cellular migration. Integrin-ligand interactions are now considered to provide physical support for cells in order to maintain cohesion, to permit the generation of traction forces to enable movement, and to organize signalling complexes to modulate differentiation and cell fate. Animal-model studies have also shown that integrins contribute to the progression of many common diseases, and have implicated them as potential therapeutic targets. The use of anti-integrin monoclonal antibodies and ligand-mimetic peptides has validated this suggestion for inflammatory, neoplastic, traumatic and infectious conditions. Thus, to understand more about the mechanisms underlying tissue organization and cellular trafficking, and to identify approaches for regulating these processes in disease, there is intense interest in determining the molecular basis of integrin function. It is important to state at the outset that the tertiary structure of the integrin dimer is unknown. Our current understanding of the molecular basis of integrin function is therefore compiled from the results of a large number of studies that have employed a wide range of complementary technologies.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 10961914 [PubMed - indexed for MEDLINE]

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12: Curr Med Chem. 1999 Oct;6(10):971-81.


Structure-activity relationships of beta-amino acid-containing integrin antagonists.

Scarborough RM.

Department of Medicinal Chemistry, COR Therapeutics, Inc., 256 East Grand Ave., S., San Francisco, CA 94080, USA.

Interest in the development of specific antagonists of the beta3 family of integrins (platelet alphaIIbbeta3 and the vitronectin receptor alphavbeta3) has been principally driven by efforts to design more potent antithrombotic agents than either aspirin or the thienopyridine-type ADP receptor modulators. The platelet fibrinogen receptor (aIIbb3) and the vitronectin receptor (alphavbeta3) bind the RGD tripeptide sequence found within adhesive ligands. Because of this, many approaches to antagonists of beta3 receptors have utilized an RGD mimetic to identify antagonists. Integrin antagonists of many structurally diverse classes have been discovered. One of the larger beta3 integrin antagonist classes employs beta-amino acids to mimic the aspartate residue of the RGD mimetic. Structure-activity investigations have revealed the potent activity of agents which have substituents appended to both the alpha and beta position of the beta-amino acid units of these antagonists. Several clinical candidates targeting platelet aIIbb3 contain these beta-amino acid units and are currently being evaluated clinically.

Publication Types:
Review

PMID: 10519908 [PubMed - indexed for MEDLINE]

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13: Proc Soc Exp Biol Med. 1999 Oct;222(1):29-38.


Platelet integrin GPIIb/IIIa: structure-function correlations. An update and lessons from other integrins.

Calvete JJ.

Instituto de Biomedicina de Valencia, CSIC, Spain. jcalvete@ibv.csic.es

Glycoprotein (GP) IIb/IIIa complex (integrin alphaIIbbeta3) is the most abundant platelet receptor. It serves as an inducible receptor for adhesive proteins and is the best-studied member of the integrin family. Its major global structural features have been elucidated mainly during the last decade. Since 1995, there has been a substantial increase in structural information on adhesion molecule domains. The crystal structures of isolated integrin I domains have been solved. Although a high resolution picture of a whole integrin molecule is not yet available, the crystal structures together with biochemical, mutagenesis and modeling data provide a useful framework for interpreting current experimental evidence on structure-function correlations of integrin molecules and for guiding further experiment. The aim of this minireview is to update a previous one summarizing recent (1995-98) functional and structural data of GPIIb/IIIa and other integrins in the perspective of an emerging model of the structure, and bidirectional signaling mechanism through, integrin alphaIIbbeta3.

Publication Types:
Review

PMID: 10510244 [PubMed - indexed for MEDLINE]

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14: Biochem Soc Trans. 1997 May;25(2):433-9.


Structure and function of the mucosal T-cell integrin alpha E beta 7.

Kilshaw PJ, Karecla P.

Department of Immunology, Babraham Institute, Cambridge, U.K.

Publication Types:
Review

PMID: 9191131 [PubMed - indexed for MEDLINE]

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15: Rinsho Byori. 1997 Feb;Suppl 104:60-72.


[Structure and function of platelet alpha IIb beta 3 integrin]

[Article in Japanese]

Suzuki H.

Publication Types:
Review

PMID: 9128366 [PubMed - indexed for MEDLINE]

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16: Mol Med Today. 1996 Jul;2(7):304-13.


Integrin adhesion receptors: structure, function and implications for biomedicine.

Newham P, Humphries MJ.

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, UK. pnewham@fs2.scg.man.ac.uk

Over the past decade, multi-disciplinary approaches have led to the discovery and characterization of several classes of adhesion molecules. Under normal conditions, these molecules provide support for cells, regulate cell migration and contain information that cells use when sensing their environment. In disease, adhesive function is frequently compromised and results in tissue disorder, aberrant cell migration and dysregulation of signalling pathways. The integrins are a major family of adhesion receptors produced by most cell types and are a means by which the cell senses its immediate environment and responds to changes in extracellular matrix composition. Recent years have seen major advances in our understanding of integrin-ligand interactions, and have revealed a structurally dynamic family of receptors capable of translating information into and out of the cell.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 8796911 [PubMed - indexed for MEDLINE]

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17: Nippon Rinsho. 1995 Jul;53(7):1623-30.


[Subclassification, molecular structure, function and ligand in integrin superfamily]

[Article in Japanese]

Matsuura N, Takada Y.

Department of Pathology II, Wakayama Medical School.

Integrins are the major family of cell surface receptors that mediate adhesion to the extracellular matrix and sometimes cell-cell adhesive interactions. These integrin-mediated adhesive interactions are involved in the regulation of many cellular functions, including embryonic development, tumor cell growth and metastasis, programmed cell death, hemostasis, inflammation, immune reaction, bone reabsorption, etc. Integrins are composed of alpha and beta transmembrane subunits selected from among 16 alpha and 8 beta subunits that heterodimerize to produce more than 20 different receptors which bind specific ligands. Ligand binding sites have been clarified by chimera integrin protein in some integrins. Integrins link to intracellular cytoskeletal complexes and bundles of actin filaments. There have been many reports about intracellular signaling pathways activated by integrin-ligand interactions.

Publication Types:
English Abstract
Review

PMID: 7629999 [PubMed - indexed for MEDLINE]

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18: Proc Soc Exp Biol Med. 1995 Apr;208(4):346-60.


On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor.

Calvete JJ.

Instituto de Química-Física Rocasolano C.S.I.C., Madrid, Spain.

Platelet membrane glycoprotein (GP) IIb/IIIa (alpha IIb beta 3), a Ca(2+)-dependent heterodimer, serves as an inducible receptor for fibrinogen and other adhesive plasma proteins, and is the most thoroughly studied integrin receptor. Intensive research during the past several years has elucidated the major features of its biosynthetic pathway, covalent structure, domain organization, and topography, and we are beginning to get an insight into the cellular mechanisms controlling integrin function. The emerging picture indicates that platelet-specific elements initiate at the cytoplasmic domains of GPIIb/IIIa a signal that leads to conformational changes within the integrin's extracellular domains and expression of the fibrinogen receptor. The simultaneous occupancy on adjacent platelets of receptors with dimeric fibrinogen molecules leads to platelet aggregation. Further structural alterations promote clustering of occupied GPIIb/IIIa complexes and their attachment to the remodelling cytoskeletal network. This interaction provides the physical link for clot retraction to occur and appears to regulate the compartmentalization, and local activation, of a multienzymatic complex which translates the ligand-binding information into time-dependent irreversibility of the fibrinogen-GPIIb/IIIa interaction. Platelet GPIIb/IIIa plays, thus, a central role in thrombus formation both in health and disease: abnormalities in the platelet adhesive mechanisms responsible for the formation of the hemostatic plug, lead to major pathophysiologic disorders, ranging from severe bleeding to thrombosis. It is, therefore, not surprising that GPIIb/IIIa has been the subject of intensive research during the last decades, since a detailed knowledge of the molecular biology and the mechanism underlying the platelet activation and aggregation processes may aid in the rational design of both an effective gene replacement therapy, and of potent and specific anti-thrombotic drugs. The aim of this minireview is to summarize many functional and structural data from different laboratories in the perspective of an emerging model that may help us to understand structure-function relationships of GPIIb/IIIa and of other members of the integrin family.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7535429 [PubMed - indexed for MEDLINE]

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19: Thromb Haemost. 1994 Jul;72(1):1-15.


Clues for understanding the structure and function of a prototypic human integrin: the platelet glycoprotein IIb/IIIa complex.

Calvete JJ.

Institut für Reproduktionsmedizin, Tierärztliche Hochschule Hannover, Germany.

The glycoprotein (GP) IIb/IIIa, a Ca(2+)-dependent heterodimer, is the major integrin on the platelet plasma membrane. On resting platelets GPIIb/IIIa is maintained in an inactive conformation and serves as a low affinity adhesion receptor for surface-coated fibrinogen, whereas upon platelet activation signals within the cytoplasma alter the receptor function of GPIIb/IIIa (inside-out signalling), which undergoes a measurable conformational change within its exoplasmic domains, and becomes a competent receptor for soluble fibrinogen and some other RGD sequence-containing plasma adhesive proteins. Upon ligand binding, further structural alterations trigger the association of receptor-occupied GPIIb/IIIa complexes with themselves within the plane of the membrane. The simultaneous binding of dimeric fibrinogen molecules to GPIIb/IIIa clusters on adjacent platelets leads to platelet aggregation, which promotes attachment of fibrinogen-GPIIb/IIIa clusters to the cytoskeleton (outside-in signalling). This, in turn, provides the necessary physical link for clot retraction to occur, and generates a cascade of intracellular biochemical reactions which result in the formation of a multiprotein signalling complex at the cytoplasmic domains of GPIIb/IIIa. Glycoprotein IIb/IIIa, also called alpha IIb beta 3 in the integrin nomenclature, plays thus a primary role in both platelet adhesion and thrombus formation at the site of vascular injury. In addition, the human glycoprotein IIb/IIIa complex is the most thoroughly studied integrin receptor, its molecular biology and major features of its primary structure having been elucidated mainly during the last six years. Furthermore, localization of functionally relevant monoclonal antibody epitopes, determination of the cross-linking sites of inhibitory peptide ligands, proteolytic dissection of the isolated integrin, and analysis of natural and artificial GPIIb/IIIa mutants have recently provided a wealth of information regarding structure-function relationships of human GPIIb/IIIa. The aim of this review is to summarize these many structural and functional data in the perspective of an emerging model. Although most of the interpretations based on structural elements of this initial biochemical model require independent confirmation, they may help us to understand the structure-function relationship of this major platelet receptor, and of other members of the integrin superfamily, as well as to perform further investigations in order to test current hypotheses.

Publication Types:
Review

PMID: 7974356 [PubMed - indexed for MEDLINE]

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20: Postepy Biochem. 1994;40(1):45-54.


[Structure and function of integrin receptors based on platelet receptor for fibrinogen]

[Article in Polish]

Cierniewski CS.

Zakład Biofizyki, Akademia Medyczna, Lódź.

Publication Types:
In Vitro
Review

PMID: 8208636 [PubMed - indexed for MEDLINE]

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21: Cancer Metastasis Rev. 1991 May;10(1):3-10.


Structure, function and biological properties of integrin alpha v beta 3 on human melanoma cells.

Cheresh DA.

Research Institute of Scripps Clinic, Dept. of Immunology, LaJolla, CA 92037.

Human melanoma represents one of the most metastatic cancers in man. The capacity of melanoma cells to invade a variety of tissues and extracellular matrices is, in part, due to their repertoire of adhesion receptors. To this end, human melanoma cells express multiple integrin cell adhesion receptors among these is the vitronectin receptor, alpha v beta 3. This adhesion receptor enables melanoma cells to attach to a wide variety of extracellular matrix components containing the sequence Arg-Gly-Asp. This review will focus on the biosynthetic, biochemical and biological properties of this receptor expressed on the surface of human melanoma cells.

Publication Types:
Review

PMID: 1717171 [PubMed - indexed for MEDLINE]

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22: Ann N Y Acad Sci. 1991;614:214-28.


Integrin structure and function in hemostasis and thrombosis.

Bennett JS.

Hematology-Oncology Section, University of Pennsylvania School of Medicine, Philadelphia 19104.

Publication Types:
Review

PMID: 2024885 [PubMed - indexed for MEDLINE]

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23: Chem Immunol. 1991;50:55-74.


Integrin alpha 4 beta 1: its structure, ligand-binding specificity and role in lymphocyte-endothelial cell interactions.

Ager A, Humphries MJ.

Department of Cell and Structural Biology, University of Manchester, UK.

Publication Types:
Review

PMID: 1786107 [PubMed - indexed for MEDLINE]

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24: Immunol Rev. 1990 Apr;114:45-65.


Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions.

Hemler ME, Elices MJ, Parker C, Takada Y.

Dana-Farber Cancer Institute, Laboratory of Immunochemistry, Division of Tumor Virology, Boston, MA 02115.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 2142475 [PubMed - indexed for MEDLINE]
 

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