Ligand Binding to GPIIb-IIIa: A Status Report

Plow, Edward F.; D’Souza, Stanley E.; Ginsberg, Mark H.

doi:10.1055/s-2007-1002571

Cited by 128 publications

(88 citation statements)

References 41 publications

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“…It seems that the Ca2'-binding motifs of the IIb subunit are organized in a manner similar to that in troponin C. Fluorescence experiments also revealed that the Caz+-binding domain(s) of the IIb subunit, when loaded with Caz+, are further stabilized by the RGD-containing peptide suggesting their involvement in the binding of this ligand. This is consistent with the known involvement of the second Caz+-binding motif of IIb in formation of the ligand binding pocket [2,4,381.…”

Section: Discussionsupporting

confidence: 90%

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Makogonenko

Yakubenko

Ingham

et al. 1996

European Journal of Biochemistry

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Thermal denaturation of platelet glycoprotein IIbIIIa (integrin aI&) was investigated by spectrofluorimetry and differential scanning calorimetry (DSC). Two forms of the protein were compared: active IIbIIIa, i.e., that fraction that binds to RGD-Sepharose, and inactive IIbIIIa, the non-binding fraction. At pH 8.5 in the presence of octyl glucoside and Ca2+ both forms exhibited a broad complex endotherm consisting of a well expressed low-temperature heat-absorption peak in the range of 40-65 "C followed by a broad peak stretching over 65-110°C. Each endotherm could be deconvoluted into at least eight transitions reflecting the melting of at least this many independently folded domains. The first two transitions in the region of the low-temperature peak had similar positions in both forms while at least some of the other transitions occurred at higher temperature in the active protein suggesting that some of the domains are more stable in the latter. When both fractions of IIbIIIa were heated in the fluorometer a sigmoidal transition was observed in the region of the first endothermic peak where the two thermolabile domains melt. This transition was destabilized by 15°C in the presence of EDTA, suggesting that these domains are formed by the 243-468 region of the IIb subunit which contains four Ca2+-binding motifs. It was further stabilized by 3°C upon addition of the G m S P K peptide in the presence of Caz+ while in EDTA the peptide had no effect. This is consistent with the involvement of Caz+-binding region in the formation of the ligand-binding site. A 66-kDa chymotryptic fragment, containing the 17-kDa NH,-terminal portion of the IIIa subunit disulfide-linked to its 50-kDa COOH-terminal portion including the cysteine-rich core, exhibited a fluorescence-detected Ca2'-independent transition in the region where the higher temperature DSC-detected transitions occur suggesting that some of the latter may be connected with the melting of the corresponding portions of IIbIIIa.Keywords : integrin ; glycoprotein IIbIIIa; fragments ; domains ; calorimetry.Platelet surface receptor glycoprotein IIbIIIa is a member of the structurally related integrin family of receptors that mediate cell-cell or cell-matrix interactions 11 -31. By mediating the fibrinogen-dependent interaction between platelets, IIbIIIa plays an essential role in platelet aggregation which is the primary mechanism of hemostatic control. All integrin receptors are composed of different variants of a and p subunits, whose combinations result in a variety of homologous non-covalently associated heterodimers [3]. Glycoprotein IIbIIIa (ar& in the integrin nomenclature) has served as a prototype to study structure/ function relationship in integrins. The IIIa v3) subunit is represented by a single chain of 762 amino acid residues while the IIb (a,,J subunit is synthesized as a single-chain polypeptide which is processed by proteolytic cleavage into a disulfidelinked heavy chain (856 residues) and light chain (149 residues) [I, 2, 41. Both IIb and IIIa subun...

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Section: Discussionsupporting

confidence: 90%

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Makogonenko

Yakubenko

Ingham

et al. 1996

European Journal of Biochemistry

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“…Platelet aggregation induced by physiological agonists is mediated by the interaction of fibrinogen with GPIIb-IIIa [1][2][3]. CRC54, like these agonists, was able to stimulate [125I]fibrinogen binding to platelets and this increase was inhibited by the anti-GPIIb-IIIa blocking antibody, CRC64, showing binding specificity towards GPIIb-IIIa.…”

Section: Resultsmentioning

confidence: 99%

“…However, agonist-induced platelet activation leads to conformational changes in GPIIb-IIIa resulting in the opening of the ligand-binding pocket, binding of fibrinogen and other RGDcontaining plasma proteins and platelet aggregation (reviews [1][2][3]). Ligand binding induces additional conformational changes which cause exposure of ligand-induced binding sites (LIBS) neoepitopes [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of platelet glycoprotein IIb‐IIIa (α_IIbβ₃‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa

et al. 1996

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“…The Gly-65-Val-74 sequence motif which forms the tip of the E strand of domain D1 and is in contact with the loop CЈ-E of domain D2 (26), most probably constitutes a major part of the ␣ IIb ␤ 3 integrin binding site on ICAM-4. Therefore, binding inhibition by RGD and FBI peptides, which bind to the ␤ 3 chain (GPIIIa) and ␣ IIb chain (GPIIb), respectively (47), suggest that ICAM-4 binds to the same or overlapping site(s) on the ␣ IIb ␤ 3 complex. It should be noticed that the G70R substitution responsible for the blood group LW a 3 LW b polymorphism (48), which corresponds to the first position of the QXXDV motif, had no effect on RBC platelet adhesion reported here, 2 suggesting that this polymorphism is neutral with regard to ICAM-4/␣ IIb ␤ 3 integrin interaction.…”

Section: Discussionmentioning

confidence: 99%

Red Cell ICAM-4 Is a Novel Ligand for Platelet-activated αIIbβ3 Integrin

Hermand¹,

Gane²,

Huet³

et al. 2003

Journal of Biological Chemistry

101

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ICAM-4 (LW blood group glycoprotein) is an erythroid-specific membrane component that belongs to the family of intercellular adhesion molecules and interactsThe main physiological function of red blood cells (RBCs), 1 which encapsulate hemoglobin, is to ensure the respiratory gases transport throughout the human body. However, the recent demonstration that mature RBCs express a growing number of adhesion molecules, many of which exhibit blood group specificities (1-3), reinforces the necessity to revisit the functional interaction of RBCs with leukocytes, platelets, and vascular endothelium under normal and pathological conditions.It is interesting that many RBC adhesion molecules contain protein domains characteristic of the immunoglobulin superfamily, suggesting some recognition function. These molecules might participate in the normal RBC physiology by playing a role during erythropoiesis (differentiation, maturation, enucleation, release), self-recognition mechanisms, red cell turnover, and cell aging through cellular interactions with counter

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Ligand Binding to GPIIb-IIIa: A Status Report

Cited by 128 publications

References 41 publications

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Stimulation of platelet glycoprotein IIb‐IIIa (α_IIbβ₃‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa

Red Cell ICAM-4 Is a Novel Ligand for Platelet-activated αIIbβ3 Integrin

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Ligand Binding to GPIIb-IIIa: A Status Report

Cited by 128 publications

References 41 publications

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Thermal Stability of Individual Domains in Platelet Glycoprotein IIbIIIa

Stimulation of platelet glycoprotein IIb‐IIIa (αIIbβ3‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa

Red Cell ICAM-4 Is a Novel Ligand for Platelet-activated αIIbβ3 Integrin

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Stimulation of platelet glycoprotein IIb‐IIIa (α_IIbβ₃‐integrin) functional activity by a monoclonal antibody to the N‐terminal region of glycoprotein IIIa