Key interactions in integrin ectodomain responsible for global conformational change detected by elastic network normal-mode analysis

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

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14 Citations (Scopus)


Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular-matrix interactions for metazoan. A group of integrins is known to perform a large-scale structural change when the protein is activated, but the activation mechanism and generality of the conformational change remain to be elucidated. We performed normal-mode analysis of the elastic network model on integrin αVβ3 ectodomain in the bent form and identified key residues that influenced molecular motions. Iterative normal-mode calculations demonstrated that the specific nonbonded interactions involving the key residues work as a snap to keep integrin in the bent form. The importance of the key residues for the conformational change was further verified by mutation experiments, in which integrin αIIbβ3 was used. The conservation pattern of amino acid residues among the integrin family showed that the characteristic pattern of residues seen around these key residues is found in the limited groups of integrin β-chains. This conservation pattern suggests that the molecular mechanism of the conformational change relying on the interactions found in integrin αVβ3 is unique to the limited types of integrins.

Original languageEnglish
Pages (from-to)2895-2908
Number of pages14
JournalBiophysical Journal
Issue number6
Publication statusPublished - 2008 Sep 15


ASJC Scopus subject areas

  • Biophysics

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