RGD induces conformational transition in purified platelet integrin GPIIb/IIIa-SDS system yielding multiple binding states for fibrinogen gamma-chain C-terminal peptide

被引：18

作者：

Mayo, KH ^{[1
]}

Fan, F ^{[1
]}

Beavers, MP ^{[1
]}

Eckardt, A ^{[1
]}

Keane, P ^{[1
]}

Hoekstra, WJ ^{[1
]}

AndradeGordon, P ^{[1
]}

机构：

[1] RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA 19477

来源：

FEBS LETTERS | 1996年 / 378卷 / 01期

关键词：

fibrinogen; peptide; platelet; integrin GPIIb/IIIa; NMR spectroscopy;

D O I：

10.1016/0014-5793(95)01418-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibrinogen gamma-chain C-terminal peptide HHLG-GAKQAGDV (gamma 12) and alpha-chain peptide GRGDSP are known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet integrin receptor GPIIb/IIIa. NMR studies of gamma 12 in the presence of purified GPIIb/IIIa in SDS/water solution have demonstrated the presence of two gamma 12 binding states, one of which is eliminated by GRGDSP (RGD) up to a RGD:gamma 12 ratio of 2:1. RGD:gamma 12 ratios greater than 2:1 produce multiple sets of gamma 12 NMR signals in TOCSY spectra. At a ratio of 4:1, two to four such resonance sets can be resolved for A405, Q407, A408, G409, D410 and V411 spin systems. The number of multiple resonances remains unchanged at ratios of 6:1 and 8:1. Addition of gamma 12 to reverse the ratio to 8:8 (1:1) has no apparent effect on the RGD-induced distribution. Results suggest that RGD irreversibly induces a conformational transition(s) in GPIIb/IIIa to produce multiple gamma 12 binding sites on the receptor.

引用

页码：79 / 82

页数：4

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