3FCS

Structure of complete ectodomain of integrin aIIBb3

Summary for 3FCS

• Entry DOI: 10.2210/pdb3fcs/pdb
• Related: 3FCU
• Descriptor: Integrin, alpha 2b, MAGNESIUM ION, Integrin beta-3, ... (11 entities in total)
• Functional Keywords: beta propeller, rossmann fold, egf domain, cell adhesion, disease mutation, glycoprotein, host-virus interaction, integrin, membrane, phosphoprotein, receptor, transmembrane, cell adhesion-immune system complex, cell adhesion-blood clotting complex, cell adhesion/blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 368902.43

Authors

Zhu, J.,Luo, B.-H.,Xiao, T.,Zhang, C.,Nishida, N.,Springer, T.A. (deposition date: 2008-11-22, release date: 2009-01-20, Last modification date: 2024-10-16)

Primary citation

Zhu, J.,Luo, B.H.,Xiao, T.,Zhang, C.,Nishida, N.,Springer, T.A.
Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces.
Mol.Cell, 32:849-861, 2008

PubMed Abstract: The complete ectodomain of integrin alpha(IIb)beta(3) reveals a bent, closed, low-affinity conformation, the beta knee, and a mechanism for linking cytoskeleton attachment to high affinity for ligand. Ca and Mg ions in the recognition site, including the synergistic metal ion binding site (SyMBS), are loaded prior to ligand binding. Electrophilicity of the ligand-binding Mg ion is increased in the open conformation. The beta(3) knee passes between the beta(3)-PSI and alpha(IIb)-knob to bury the lower beta leg in a cleft, from which it is released for extension. Different integrin molecules in crystals and EM reveal breathing that appears on pathway to extension. Tensile force applied to the extended ligand-receptor complex stabilizes the closed, low-affinity conformation. By contrast, an additional lateral force applied to the beta subunit to mimic attachment to moving actin filaments stabilizes the open, high-affinity conformation. This mechanism propagates allostery over long distances and couples cytoskeleton attachment of integrins to their high-affinity state.

PubMed: 19111664
DOI: 10.1016/j.molcel.2008.11.018

Experimental method

X-RAY DIFFRACTION (2.55 Å)