2VDQ: Integrin Alphaiibbeta3 Headpiece Bound To A Chimeric Fibrinogen Gamma Chain Peptide, Hhlggakqrgdv

Citation:
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 and thrombosis.
PDB ID: 2VDQDownload
MMDB ID: 66417
PDB Deposition Date: 2007/10/10
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.59  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 2VDQ: pentameric; determined by author and by software (PQS)
Molecular Components in 2VDQ
Label Count Molecule
Proteins (5 molecules)
1
Integrin Alpha-iib(Gene symbol: ITGA2B)
Molecule annotation
1
Integrin Beta-3(Gene symbol: ITGB3)
Molecule annotation
1
Monoclonal Antibody 10e5 Heavy Chain
Molecule annotation
1
Monoclonal Antibody 10e5 Light Chain
Molecule annotation
1
Fibrinogen, Gamma Polypeptide
Molecule annotation
Chemicals (24 molecules)
1
2
2
6
3
7
4
1
5
8
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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