Valeria Vasquez, Marcos Sotomayor, D. Marien Cortes, Benoit Roux, Klaus
Schulten, and Eduardo Perozo.
Three dimensional architecture of membrane-embedded MscS in the
closed conformation.
Journal of Molecular Biology, 378:55-70, 2008.
(PMC: 2703500)
VASQ2008
The mechanosensitive channel of small conductance (MscS) is part of a coordinated response to osmotic challenges in E. coli. MscS opens as a result of membrane tension changes, thereby releasing small solutes and effectively acting as an osmotic safety valve. Both, the functional state depicted by its crystal structure and its gating mechanism remain unclear. Here, we combine site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy, and molecular dynamics simulations with novel energy restraints based on experimental EPR data to investigate the native transmembrane and periplasmic molecular architecture of closed MscS in a lipid bilayer. In the closed conformation, MscS shows a more compact transmembrane domain than in the crystal structure, characterized by a realignment of the transmembrane segments towards the normal of the membrane. The previously unresolved NH2-terminus forms a short helical hairpin capping the extracellular ends of TM1 and TM2 and in close interaction with the bilayer surface. The present three-dimensional model of membrane-embedded MscS in the closed state represents a key step in determining the molecular mechanism of MscS gating.
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