Glycoprotein lib peptide 656–667 mimics the fibrinogen γ chain 402–411 binding site on platelet integrin GPIIb/IIIa

FEBS Letters

Schäfer, Wolfram⁴  Calvete, Juan J.²  Niewiarowski, Stefan³  McLane, Mary Ann³  Rivas, Germán¹ 

[1] Biozentrum, Basel, Switzerland;Instituto de Química-Física ‘Rocasolano’ CSIC, Madrid, Spain;Department of Physiology, Temple University School of Medicine, Philadelphia, USA;Max Planck Institut für Biochemie, Germany

关键词: Platelet;    GPIIb/IIIa;    Platelet aggregation;    Fibrinogen binding site;    Peptide synthesis;    Equilibrium sedimentation;   

DOI  :  10.1016/0014-5793(93)80454-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human integrin glycoprotein IIb/IIIa complex plays a central role in haemostasis as an inducible receptor for fibrinogen and other adhesive proteins at the platelet plasma membrane. Current evidence indicates that the ligand-binding domain of GPIIb/IIIa is discontinuous and placed at the subunit interface. Here we show that a synthetic peptide containing the polypeptide stretch GPIIb 656–667, which is hidden within the resting platelet GPIIb/IIIa heterodimer but becomes exposed following platelet activation with thrombin, binds to soluble fibrinogen (n = 2.3 ± 1.3; K _d = 2 ± 0.8 × 10⁻⁵ M). This interaction is Ca²⁺-independent and can be partially inhibited with synthetic fibrinogen γ-chain peptide 400–411 but not with GRGDS. In addition, peptide GPIIb 656–667 inhibits in a dose-dependent manner the aggregation of activated platelets (IC₅₀ = 170μM). Altogether, our results indicate that the GPIIb 656–667 region may form part of the inducible fibrinogen binding site and may not overlap with the integrin RGD-recognition domain.

【 授权许可】

Unknown