title: Stress sensor triggers conformational response of the integral membrane protein microsomal glutathione transferase 1.
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.
authors.affiliation: Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Busenlehner
authors.forename: Simona G
authors.initials: SG
authors.lastname: Codreanu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Holm
authors.forename: Priyaranjan
authors.initials: P
authors.lastname: Bhakat
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.forename: Ralf
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Richard N
authors.initials: RN
authors.lastname: Armstrong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D041961:Deuterium Exchange Measurement; D005033:Ethylmaleimide / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008565:Membrane Proteins; D010446:Peptide Fragments; D011510:Proteolipids; C122107:microsomal glutathione S-transferase-I; D005982:Glutathione Transferase; D005978:Glutathione; D005033:Ethylmaleimide