The complete ectodomain of integrin αIIbβ3 reveals a bent, closed, low-affinity conformation, the β 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 β3 knee passes between the β3-PSI and αIIb-knob to bury the lower β 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 β 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. © 2008 Elsevier Inc. All rights reserved.
Publication Source (Journal or Book title)
Zhu, J., Luo, B., Xiao, T., Zhang, C., Nishida, N., & Springer, T. (2008). Structure of a Complete Integrin Ectodomain in a Physiologic Resting State and Activation and Deactivation by Applied Forces. Molecular Cell, 32 (6), 849-861. https://doi.org/10.1016/j.molcel.2008.11.018