TCB Publications - Abstract

Wei Chen, Jizhong Lou, Jen Hsin, Klaus Schulten, Stephen C. Harvey, and Cheng Zhu. Molecular dynamics simulations of forced unbending of integrin αVβ3. PLoS Computational Biology, 7(2):e1001086, 2011. (13 pages). (PMC: 3040657)

CHEN2011 Integrins undergo large conformational changes during activation, but the dynamic processes and pathways remain poorly understood. We used molecular dynamics to simulate forced unbending of the complete integrin $\alpha_{V}\beta_{3}$ ectodomain in both unliganded and liganded forms. Pulling the $\beta$A domain or the bound ligand readily induced change of the integrin from a bent to extended conformation. Interactions at the interfaces between the hybrid and $\beta$ tail domains and between the hybrid and epidermal growth factor 4 domains formed the major energy barrier along the unbending pathway, which could be overcome spontaneously in 1 $\micro$s to yield a partially- extended conformation that tended to rebend. By comparison, a fully-extended conformation was stable partially due at least partly to a new coordination between the $\alpha_V$ Asp457 and the $\alpha$-genu metal ion. These results show how easy force can induce $\alpha_{V}\beta_{3}$ extension and suggest respective interactions that keep this integrin bent and extended.

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