Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel.
Mechanosensitive ion channels play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. The MscL family of large-conductance mechanosensitive channels is widely distributed among prokaryotes and may participate in the regulation of osmotic pressure changes within the cell. In an effort to better understand the structural basis for the function of these channels, the structure of the MscL homolog from Mycobacterium tuberculosis was determined by x-ray crystallography to 3.5 angstroms resolution. This channel is organized as a homopentamer, with each subunit containing two transmembrane alpha helices and a third cytoplasmic alpha helix. From the extracellular side, a water-filled opening approximately 18 angstroms in diameter leads into a pore lined with hydrophilic residues which narrows at the cytoplasmic side to an occluded hydrophobic apex that may act as the channel gate. This structure may serve as a model for other mechanosensitive channels, as well as the broader class of pentameric ligand-gated ion channels exemplified by the nicotinic acetylcholine receptor.
Chang
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Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, 147-75CH, California Institute of Technology, Pasadena, CA 91125, USA.
Spencer
R H
RH
Lee
A T
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Barclay
M T
MT
Rees
D C
DC
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry; D003001:Cloning, Molecular; D003460:Crystallization; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013696:Temperature
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; D008024:Ligands; C086596:MscL protein, E coli; C116377:Tb-MscL protein, Mycobacterium tuberculosis