On the structure of the N-terminal domain of the MscL channel

Helical bundle or membrane interface

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The mechanosensitive channel of large conductance, MscL, serves as a biological emergency release valve protecting bacteria from acute osmotic downshock and is to date the best characterized mechanosensitive channel. A wellrecognized and supported model for Escherichia coli MscL gating proposes that the N-terminal 11 amino acids of this protein form a bundle of amphipathic helices in the closed state that functionally serves as a cytoplasmic second gate. However, a recently reexamined crystal structure of a closed state of the Mycobacterium tuberculosis MscL shows these helices running along the cytoplasmic surface of the membrane. Thus, it is unclear if one structural model is correct or if they both reflect valid closed states. Here, we have systematically reevaluated this region utilizing cysteine-scanning, in vivo functional characterization, in vivo SCAM, electrophysiological studies, and disulfide-trapping experiments. The disulfide-trapping pattern and functional studies do not support the helical bundle and second-gate hypothesis but correlate well with the proposed structure for M. tuberculosis MscL. We propose a functional model that is consistent with the collective data.

Original languageEnglish (US)
Pages (from-to)2283-2291
Number of pages9
JournalBiophysical Journal
Volume95
Issue number5
DOIs
StatePublished - Sep 1 2008

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Mycobacterium tuberculosis
Disulfides
Membranes
Structural Models
Cysteine
Emergencies
Cell Membrane
Escherichia coli
Bacteria
Amino Acids
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

On the structure of the N-terminal domain of the MscL channel : Helical bundle or membrane interface. / Iscla, Irene; Wray, Robin; Blount, Paul.

In: Biophysical Journal, Vol. 95, No. 5, 01.09.2008, p. 2283-2291.

Research output: Contribution to journalArticle

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