Structure of a Complete Integrin Ectodomain in a Physiologic Resting State and Activation and Deactivation by Applied Forces
- Harvard-Med
The complete ectodomain of integrin {alpha}{sub IIb}{beta}{sub 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}{sub 3} knee passes between the {beta}{sub 3}-PSI and {alpha}{sub 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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007114
- Journal Information:
- Mol. Cell, Journal Name: Mol. Cell Journal Issue: (6) ; 12, 2008 Vol. 32; ISSN 1097-2765
- Country of Publication:
- United States
- Language:
- ENGLISH
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