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Published December 18, 1998 | public
Journal Article

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

Abstract

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 fromMycobacterium 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 α helices and a third cytoplasmic α 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.

Additional Information

© 1998 American Association for the Advancement of Science. 29 October 1998; Accepted 16 November 1998. We thank A. Chirino for advice and computer support, J. G. Spencer for technical assistance, S. Gordon of the Institut Pasteur (Paris, France) for his kind gift of genomic DNA from M. tuberculosis, C. Kung and P. C. Moe from the University of Wisconsin-Madison for several cloned mscL homologs and for the E. coli knockout mutant for mscL, A. Okabe of the Kagawa Medical School (Kagawa, Japan) for providing cloned DNA of mscL from C. perfringens, and D. Dougherty and H. Lester for helpful discussions. We also thank the staff at the Stanford Synchrotron Radiation Laboratory (SSRL) and the Advanced Light Source (ALS) for their help in data collection. The synchrotron rotation camera facilities are supported by the U.S. Department of Energy (ALS and SSRL) and NIH (SSRL). G.C. and R.H.S. were supported by NIH postdoctoral fellowship grant GM18486 and an Amgen postdoctoral fellowship, respectively, during the initial stages of this project. Supported by the Howard Hughes Medical Institute. Protein Data Bank identifier for Tb-MscL is 1MSL.

Additional details

Created:
August 19, 2023
Modified:
October 18, 2023