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Science 18 December 1998:
Vol. 282. no. 5397, pp. 2220 - 2226
DOI: 10.1126/science.282.5397.2220

Research Articles

Structure of the MscL Homolog from Mycobacterium tuberculosis: A Gated Mechanosensitive Ion Channel

Geoffrey Chang, * Robert H. Spencer, * Allen T. Lee, Margaret T. Barclay, Douglas C. Rees dagger

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.

Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, 147-75CH, California Institute of Technology, Pasadena, CA 91125, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: dcrees{at}caltech.edu


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