Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel

Michelle D. Edwards, Yuezhou Li, Sanguk Kim, Samantha Miller, Wendy Bartlett, Susan Black, Sally Dennison, Irene Iscla, Paul Blount, James U. Bowie, Ian R. Booth

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

The crystal structure of an open form of the Escherichia coli MscS mechanosensitive channel was recently solved. However, the conformation of the closed state and the gating transition remain uncharacterized. The pore-lining transmembrane helix contains a conserved glycine- and alanine-rich motif that forms a helix-helix interface. We show that introducing 'knobs' on the smooth glycine face by replacing glycine with alanine, and substituting conserved alanines with larger residues, increases the pressure required for gating. Creation of a glycine-glycine interface lowers activation pressure. The importance of residues Gly104, Ala106 and Gly108, which flank the hydrophobic seal, is demonstrated. A new structural model is proposed for the closed-to-open transition that involves rotation and tilt of the pore-lining helices. Introduction of glycine at Ala106 validated this model by acting as a powerful suppressor of defects seen with mutations at Gly104 and Gly108.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalNature Structural and Molecular Biology
Volume12
Issue number2
DOIs
StatePublished - Feb 20 2005

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Glycine
Alanine
Pressure
Structural Models
Escherichia coli
Mutation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Edwards, M. D., Li, Y., Kim, S., Miller, S., Bartlett, W., Black, S., ... Booth, I. R. (2005). Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel. Nature Structural and Molecular Biology, 12(2), 113-119. https://doi.org/10.1038/nsmb895

Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel. / Edwards, Michelle D.; Li, Yuezhou; Kim, Sanguk; Miller, Samantha; Bartlett, Wendy; Black, Susan; Dennison, Sally; Iscla, Irene; Blount, Paul; Bowie, James U.; Booth, Ian R.

In: Nature Structural and Molecular Biology, Vol. 12, No. 2, 20.02.2005, p. 113-119.

Research output: Contribution to journalArticle

Edwards, MD, Li, Y, Kim, S, Miller, S, Bartlett, W, Black, S, Dennison, S, Iscla, I, Blount, P, Bowie, JU & Booth, IR 2005, 'Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel', Nature Structural and Molecular Biology, vol. 12, no. 2, pp. 113-119. https://doi.org/10.1038/nsmb895
Edwards, Michelle D. ; Li, Yuezhou ; Kim, Sanguk ; Miller, Samantha ; Bartlett, Wendy ; Black, Susan ; Dennison, Sally ; Iscla, Irene ; Blount, Paul ; Bowie, James U. ; Booth, Ian R. / Pivotal role of the glycine-rich TM3 helix in gating the MscS mechanosensitive channel. In: Nature Structural and Molecular Biology. 2005 ; Vol. 12, No. 2. pp. 113-119.
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