Cargando…

Key Interactions in Integrin Ectodomain Responsible for Global Conformational Change Detected by Elastic Network Normal-Mode Analysis

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Matsumoto, Atsushi, Kamata, Tetsuji, Takagi, Junichi, Iwasaki, Kenji, Yura, Kei
Formato: Texto
Lenguaje:English
Publicado: The Biophysical Society 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527288/
https://www.ncbi.nlm.nih.gov/pubmed/18515366
http://dx.doi.org/10.1529/biophysj.108.131045
Descripción
Sumario: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 α(V)β(3) 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 α(IIb)β(3) 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 α(V)β(3) is unique to the limited types of integrins.