Stress Sensor Triggers Conformational Response of the Integral Membrane Protein Microsomal Glutathione Transferase 1

• Published in: Biochemistry (Easton) 2004-09, Vol.43 (35), p.11145-11152
• Main Authors: Busenlehner, Laura S., Codreanu, Simona G., Holm, Peter J., Bhakat, Priyaranjan, Hebert, Hans, Morgenstern, Ralf, Armstrong, Richard N.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Crystallography, X-Ray; Deuterium Exchange Measurement; Ethylmaleimide - chemistry; Glutathione - chemistry; Glutathione Transferase - chemistry; Glutathione Transferase - metabolism; Glutathione Transferase - ultrastructure; Kinetics; Male; Mass Spectrometry; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membrane Proteins - ultrastructure; Microsomes, Liver - enzymology; Molecular Sequence Data; Natural Sciences; Naturvetenskap; Oxidative Stress; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Conformation; Proteolipids - chemistry; Proteolipids - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 0006-2960; 1520-4995; 1520-4995
• DOI: 10.1021/bi048716k

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.