Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3.

The Journal of Cell Biology
Timothy A SpringerTsan Xiao

Abstract

Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin alpha(IIb)beta(3) on platelets, resulting in platelet aggregation. alpha(v)beta(3) binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's alpha subunit. alpha(IIb)beta(3) also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the gamma subunit (gammaC peptide). These distinct modes of fibrinogen binding enable alpha(IIb)beta(3) and alpha(v)beta(3) to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin alpha(IIb)beta(3)-gammaC peptide interface, and, for comparison, integrin alpha(IIb)beta(3) bound to a lamprey gammaC primordial RGD motif. Compared with RGD, the GAKQAGDV motif in gammaC adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg(2+) ion binds the gammaC Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca(2+) ion binds the gammaC C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered gammaC peptide enhances our understanding of the involvement of gammaC peptide and integrin alpha(IIb)beta(3) in hemostasis a...Continue Reading

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Citations

Oct 18, 2012·Journal of Thrombosis and Thrombolysis·Henry E SpeichLisa K Jennings
Sep 11, 2010·Biochemistry·Roy R HantganSusan T Lord
Oct 31, 2012·Biochemistry·Xianchi DongTimothy A Springer
Jun 30, 2009·Nature Structural & Molecular Biology·Benjamin BishopChristian Siebold
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·YouDong PanJianFeng Chen
Jul 16, 2011·The Journal of Biological Chemistry·Timmy KendallThomas A Bunch
Jun 2, 2012·The Journal of Biological Chemistry·Ryoko Sato-NishiuchiKiyotoshi Sekiguchi
Nov 21, 2008·The Journal of Biological Chemistry·Bing-Hao LuoTimothy A Springer
Jun 27, 2013·The Journal of Cell Biology·Jieqing ZhuTimothy A Springer
Mar 12, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kemin TanJack Lawler
May 19, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas SchürpfJia-Huai Wang
Oct 25, 2011·PloS One·Bhanupratap ChouhanKonstantin Denessiouk
Dec 14, 2012·PloS One·David P SargeantMartin R Schiller
Nov 11, 2014·Nature Structural & Molecular Biology·Xianchi DongTimothy A Springer
Jan 5, 2014·The Journal of Cell Biology·Mehmet SenTimothy A Springer
Mar 28, 2012·The Journal of Cell Biology·Masamichi NagaeJunichi Takagi
Jan 11, 2012·The Journal of Cell Biology·Yamei YuTimothy A Springer
Dec 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wei Xia, Timothy A Springer
Feb 14, 2015·Bioorganic & Medicinal Chemistry Letters·Yawen WangYiping Li
Dec 2, 2011·Current Opinion in Cell Biology·Timothy A Springer, Michael L Dustin
Feb 13, 2015·Analytical Chemistry·Jiao ZhaiXueyun Gao
Mar 5, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mehmet Sen, Timothy A Springer
Nov 22, 2014·Thrombosis and Haemostasis·Róisín MoriartyDermot Cox
Jun 26, 2009·Journal of Thrombosis and Haemostasis : JTH·R F DoolittleD Wilcox
Feb 27, 2016·Organic & Biomolecular Chemistry·M Pilkington-MiksaL Manzoni
Dec 25, 2009·The EMBO Journal·Can XieTimothy A Springer
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Sep 15, 2015·Journal of Medicinal Chemistry·Pavel G PolishchukAlexandre Varnek
Jan 24, 2009·Biochimica Et Biophysica Acta·Mark S JohnsonDonald Gullberg
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·B S Coller

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Methods Mentioned

BETA
x-ray diffraction
amidation

Software Mentioned

TLS Motion Determination
MolProbity
PRODRG2
ADMIDAS
CNS
MIDAS
Coot
BlastP
HKL2000
Xpleo

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