Three-Dimensional Architecture of Membrane-Embedded MscS in the Closed Conformation

Valeria Vásquez, Marcos Sotomayor, D. Marien Cortes, Benoît Roux, Klaus Schulten, Eduardo Perozo

Research output: Contribution to journalArticle

Abstract

The mechanosensitive channel of small conductance (MscS) is part of a coordinated response to osmotic challenges in Escherichia coli. MscS opens as a result of membrane tension changes, thereby releasing small solutes and effectively acting as an osmotic safety valve. Both the functional state depicted by its crystal structure and its gating mechanism remain unclear. Here, we combine site-directed spin labeling, electron paramagnetic resonance spectroscopy, and molecular dynamics simulations with novel energy restraints based on experimental electron paramagnetic resonance data to investigate the native transmembrane (TM) and periplasmic molecular architecture of closed MscS in a lipid bilayer. In the closed conformation, MscS shows a more compact TM domain than in the crystal structure, characterized by a realignment of the TM segments towards the normal of the membrane. The previously unresolved NH2-terminus forms a short helical hairpin capping the extracellular ends of TM1 and TM2 and is in close interaction with the bilayer interface. The present three-dimensional model of membrane-embedded MscS in the closed state represents a key step in determining the molecular mechanism of MscS gating.

Original languageEnglish (US)
Pages (from-to)55-70
Number of pages16
JournalJournal of Molecular Biology
Volume378
Issue number1
DOIs
StatePublished - Apr 18 2008

Keywords

  • electron paramagnetic resonance
  • ion channels
  • mechanotransduction
  • molecular dynamics
  • spin-labeling

ASJC Scopus subject areas

  • Virology

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