Snap residues for integrin activation identified by elastic network normal mode analysis

Matsumoto, Atsushi; Kamata, Tetsuji*; Iwasaki, Kenji*; Takagi, Junichi*; Yura, Kei

Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular matrix interactions for metazoan. A group of integrins are known to perform a large-scale structural change when they are activated, but their mechanism and generality of the conformational change in other integrins remain to be elucidated. We performed normal mode analysis based on the elastic network models of integrin in the bent form to identify key residues dominating the molecular motions toward activation. We simulated the large conformational change of integrin from the bent to the extended forms by iterative normal mode calculations and demonstrated that specific non-bonded interactions involving the key residues work as a snap to lock integrin in the bent form. The importance of the key residues for the conformational change was verified by mutation experiments.