細胞はメカノストレスをどのように感知するのか?(セミナー「生物のストレス受容のメカニズム-分子レベルから細胞レベルまで-」)

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Virtually every cell responds to mechanical stimuli, by which cells can regulate their growth, shape, motility and differentiation. Mechanosensors are the major player in this cell function and mechanosensitive (MS) channels are the only established molecular class of mechanosensors to date. Among them, bacterial MscL is the best studied one owing to its resolved 3D structure. MscL is activated (opened) simply by tension increase in the plasma membrane, contributing to the cell volume regulation against hyopotonic challenge. To explore the biophysical mechanisms of MscL activation, we performed molecular dynamics (MD) simulations of structural changes of the MscL protein in response to tension increase. We found that MscL senses the tension increase mainly with Phe78 at the lipid-water interface, which induces a subtle change in the channel gate composed of hydrophobic amino acids that stabilizes the closed state of MscL. MscL opening is triggered by this subtle change and is accelerated by the penetration of water molecules into the gate region.
2011-04-15