Stress sensor triggers conformational response of the integral membrane protein microsomal glutathione transferase 1 |
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Authors: | Busenlehner Laura S Codreanu Simona G Holm Peter J Bhakat Priyaranjan Hebert Hans Morgenstern Ralf Armstrong Richard N |
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Affiliation: | Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. |
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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. |
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