Stress sensor triggers conformational response of the integral membrane protein microsomal glutathione transferase 1

Research output: Contribution to journalArticle

Abstract

Microsomal glutathione (GSH) transferase 1 (MGST1) is a trimeric, integral membrane protein involved in cellular response to chemical or oxidative stress. The cytosolic domain of MGST1 harbors the GSH binding site and a cysteine residue (C49) that acts as a sensor of oxidative and chemical stress. Spatially resolved changes in the kinetics of backbone amide H/D exchange reveal that the binding of a single molecule of GSH/trimer induces a cooperative conformational transition involving movements of the transmembrane helices and a reordering of the cytosolic domain. Alkylation of the stress sensor preorganizes the helices and facilitates the cooperative transition resulting in catalytic activation.

Details

Authors
  • L S Busenlehner
  • S G Codreanu
  • P J Holm
  • P Bhakat
  • Hans Hebert
  • R Morgenstern
  • R N Armstrong
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
Original languageEnglish
Pages (from-to)11145-11152
JournalBiochemistry
Volume43
Issue number35
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes