Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3
Abstract
Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin {alpha}{sub IIb}{beta}{sub 3} on platelets, resulting in platelet aggregation. {alpha}{sub v}{beta}{sub 3} binding fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's {alpha} subunit. {alpha}{sub IIb}{beta}{sub 3} also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the {gamma} subunit ({gamma}C peptide). These distinct modes of fibrinogen binding enable {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub v}{beta}{sub 3} to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin {alpha}{sub IIb}{beta}{sub 3}-{gamma}C peptide interface, and, for comparison, integrin {alpha}{sub IIb}{beta}{sub 3} bound to a lamprey {gamma}C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in {gamma}C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg{sup 2+} ion binds the {gamma}C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca{sup 2+} ion binds the {gamma}C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered {gamma}C peptide enhances our understanding of the involvement of {gamma}C peptide and integrin {alpha}{sub IIb}{beta}{sub 3} in hemostasis and thrombosis.
- Authors:
-
- Harvard-Med
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1006917
- Resource Type:
- Journal Article
- Journal Name:
- J. Cell Biol.
- Additional Journal Information:
- Journal Volume: 182; Journal Issue: (4) ; 2008; Journal ID: ISSN 0021-9525
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ADHESION; AGGLOMERATION; BLOOD; CONFIGURATION; CRYSTAL STRUCTURE; DATA; FIBRINOGEN; FUNCTIONS; IONS; LIGANDS; METALS; PEPTIDES; THROMBOSIS
Citation Formats
Springer, Timothy A, Zhu, Jianghai, and Xiao, Tsan. Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3. United States: N. p., 2009.
Web. doi:10.1083/jcb.200801146.
Springer, Timothy A, Zhu, Jianghai, & Xiao, Tsan. Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3. United States. https://doi.org/10.1083/jcb.200801146
Springer, Timothy A, Zhu, Jianghai, and Xiao, Tsan. 2009.
"Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3". United States. https://doi.org/10.1083/jcb.200801146.
@article{osti_1006917,
title = {Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3},
author = {Springer, Timothy A and Zhu, Jianghai and Xiao, Tsan},
abstractNote = {Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin {alpha}{sub IIb}{beta}{sub 3} on platelets, resulting in platelet aggregation. {alpha}{sub v}{beta}{sub 3} binding fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's {alpha} subunit. {alpha}{sub IIb}{beta}{sub 3} also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the {gamma} subunit ({gamma}C peptide). These distinct modes of fibrinogen binding enable {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub v}{beta}{sub 3} to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin {alpha}{sub IIb}{beta}{sub 3}-{gamma}C peptide interface, and, for comparison, integrin {alpha}{sub IIb}{beta}{sub 3} bound to a lamprey {gamma}C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in {gamma}C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg{sup 2+} ion binds the {gamma}C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca{sup 2+} ion binds the {gamma}C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered {gamma}C peptide enhances our understanding of the involvement of {gamma}C peptide and integrin {alpha}{sub IIb}{beta}{sub 3} in hemostasis and thrombosis.},
doi = {10.1083/jcb.200801146},
url = {https://www.osti.gov/biblio/1006917},
journal = {J. Cell Biol.},
issn = {0021-9525},
number = (4) ; 2008,
volume = 182,
place = {United States},
year = {Mon Jan 12 00:00:00 EST 2009},
month = {Mon Jan 12 00:00:00 EST 2009}
}