4hwa | pdb_00004hwa
Crystal Structure of Escherichia coli MscS Wildtype (Open State)
Structural highlights
Function[MSCS_ECOLI] Mechanosensitive channel that participates in the regulation of osmotic pressure changes within the cell, opening in response to stretch forces in the membrane lipid bilayer, without the need for other proteins. Forms an ion channel of 1.0 nanosiemens conductance with a slight preference for anions. The channel is sensitive to voltage; as the membrane is depolarized, less tension is required to open the channel and vice versa. The channel is characterized by short bursts of activity that last for a few seconds. The channel pore is formed by TM3 and the loop between TM2 and TM3. After a sharp turn at Gly-113, an alpha-helix (residues 114-127) is oriented nearly parallel to the plane of the putative lipid bilayer. On the intracellular side of the channel, the permeation pathway of MscS does not connect directly to the cytoplasm but instead opens to a large chamber that is connected to the cytoplasm. This chamber resembles a molecular filter that could serve to prescreen large molecules before they are allowed passage to the transmembrane pore. The TM1 and TM2 helices appear to be likely candidates for mediating the tension and voltage sensitivities of MscS. Gating requires large rearrangements of at least the C-terminus. Publication Abstract from PubMedThe mechanosensitive channel of small conductance (MscS) contributes to the survival of bacteria during osmotic downshock by transiently opening large diameter pores for the efflux of cellular contents before the membrane ruptures. Two crystal structures of the Escherichia coliMscS are currently available, the wild type protein in a non-conducting state at 3.7 A resolution(Bass et al., Science 298, 1582 (2002)) and the Ala106Val variant in an open state at 3.45 A resolution (Wang et al., Science 321, 1179 (2008)). Both structures used protein solubilized in the detergent fos-choline-14. We report here crystal structures of MscS from Escherichia coli and Helicobacter pylori solubilized in the detergent beta-dodecylmaltoside (DDM) at resolutions of 4.4 and 4.2 A, respectively. While the cytoplasmic domains are unchanged in these structures, distinctconformations of the transmembrane domains are observed. Intriguingly, DDM solubilized wild type E. coliMscSadopts the open state structure of A106V E. coliMscS, while H. pyloriMscS resembles the non-conducting state structure observed for fos-choline-14 solubilized E. coliMscS. These results highlight the sensitivity of membrane protein conformational equilibria to variationsin detergent, crystallization conditions and protein sequence. Open and shut: Crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from E. coli and H. pylori at 4.4 A and 4.1 A resolution.,Lai JY, Poon YS, Kaiser JT, Rees DC Protein Sci. 2013 Jan 22. doi: 10.1002/pro.2222. PMID:23339071[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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