Abstract
MscL is the mechanosensitive channel that is ubiquitously found among bacteria. Since MscL open by membrane tension in its purified form, MscL probably senses the tension of membrane directly. Cloning MscL gene revealed that MscL consists of 136 amino acid monomer. Crystal structure of MscL showed that MscL is a homopentamer of subunit that has two transmembrane domain, M1 and M2. The clue to the interaction that stabilizes the closed channel or causes channel opening has been obtained through random and site-directed mutagenesis study. Isolation of mutant channel that opens with little tension showed that mutations in glycines of M1 decrease the threshold. One-by-one substitutions of Gly-22, which resides within channel pore constriction, with all other amino acid indicate that hydrophobic interaction within constriction keep the channel in the closed state. Thus, the exposure of the hydrophobic residues in the constriction probably serves as the energy barrier that should be overcome by membrane tension during gating. On the other hand, mutagenesis study of the residues in the lipid-protein interface showed that the hydrophilic substitution at the periplasmic ends of M1 or M2 causes loss of function. This finding suggests that the residues at the periplasmic ends perceive the negative pressure from the membrane through hydrophobic interaction. Thus, pulling the periplasmic ends of M1 apart from the molecular fivefold axis while holding the cytoplasmic ends of M1 together may cause the tilting of M1 and initiate the channel opening. [Jpn J Physiol 54 Suppl:S20 (2004)]
