The gating mechanism of the large mechanosensitive channel MscL

The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane-embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating....

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2001-02, Vol.409 (6821), p.720-724
Main Authors: Sukharev, S., Betanzos, M., Chiang, C. S., Guy, H. R.
Format: Article
Language:English
Subjects:
Bacteria
Bacteriology
Biological and medical sciences
Biomechanical Phenomena
Crystals
Cysteine - metabolism
Disulfides - metabolism
Escherichia coli Proteins
Fundamental and applied biological sciences. Psychology
Ion Channel Gating
Ion Channels - metabolism
Life Sciences (General)
Membranes
Microbiology
Models, Biological
Models, Molecular
Mycobacterium tuberculosis
Mycobacterium tuberculosis - metabolism
Permeability, membrane transport, intracellular transport
Protein Conformation
Space life sciences
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane-embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating. Here we develop structural models in which a cytoplasmic gate is formed by a bundle of five amino-terminal helices (S1), previously unresolved in the crystal structure. When membrane tension is applied, the transmembrane barrel expands and pulls the gate apart through the S1-M1 linker. We tested these models by substituting cysteines for residues predicted to be near each other only in either the closed or open conformation. Our results demonstrate that S1 segments form the bundle when the channel is closed, and crosslinking between S1 segments prevents opening. S1 segments interact with M2 when the channel is open, and crosslinking of S1 to M2 impedes channel closing. Gating is affected by the length of the S1-M1 linker in a manner consistent with the model, revealing critical spatial relationships between the domains that transmit force from the lipid bilayer to the channel gate.
ISSN:0028-0836
1476-4687
DOI:10.1038/35055559