An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating

Yuezhou Li, Robin Wray, Christina Eaton, Paul Blount

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Mechanosensation, the ability to detect mechanical forces, underlies the senses of hearing, balance, touch, and pain, as well as renal and cardiovascular regulation. Although the sensors are thought to be channels, relatively little is known about eukaryotic mechanosensitive channels or their molecular mechanisms. Thus, because of its tractable nature, a bacterial mechanosensitive channel that serves as an in vivo osmotic "emergency release valve," MscL, has become a paradigm of how a mechanosensitive channel can sense and respond to membrane tension. Here, we have determined the structural rearrangements and interactions between transmembrane domains of MscL that occur upon gating. We utilize an electrostatic repulsion test: If two residues approach upon gating we predicted that substituting like-charges at those sites would inhibit gating. The in vivo growth and viability and in vitro vesicular flux and electrophysiological data all support the hypothesis that residues G26 and I92 directly interact upon gating. The resulting model predicted other interacting residues. One of these sets, V23 and I96, was confirmed to truly interact upon gating by disulfide trapping as well as the electrostatic repulsion test. Together, the data strongly suggest a model for structural transitions and residue-residue proximities that occur upon MscL gating.

Original languageEnglish (US)
Pages (from-to)2197-2204
Number of pages8
JournalFASEB Journal
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2009

Keywords

  • Disulfide trapping
  • Electrostatic repulsion
  • MTS reagents
  • Mechanosensation
  • Osmotic regulation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'An open-pore structure of the mechanosensitive channel MscL derived by determining transmembrane domain interactions upon gating'. Together they form a unique fingerprint.

  • Cite this