Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone
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Author(s)
Jost, Marco
Cracan, Valentin
Hubbard, Paul A.
Banerjee, Ruma
Drennan, Catherine L
Date Issued
February 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Jost, Marco, Valentin Cracan, Paul A. Hubbard, Ruma Banerjee, and Catherine L. Drennan. “Visualization of a Radical B[subscript 12] Enzyme with Its G-Protein Chaperone.” Proc Natl Acad Sci USA 112, no. 8 (February 9, 2015): 2419–2424.
Version
Final published version
Abstract
G-protein metallochaperones ensure fidelity during cofactor assembly for a variety of metalloproteins, including adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase and hydrogenase, and thus have both medical and biofuel development applications. Here, we present crystal structures of IcmF, a natural fusion protein of AdoCbl-dependent isobutyryl-CoA mutase and its corresponding G-protein chaperone, which reveal the molecular architecture of a G-protein metallochaperone in complex with its target protein. These structures show that conserved G-protein elements become ordered upon target protein association, creating the molecular pathways that both sense and report on the cofactor loading state. Structures determined of both apo- and holo-forms of IcmF depict both open and closed enzyme states, in which the cofactor-binding domain is alternatively positioned for cofactor loading and for catalysis. Notably, the G protein moves as a unit with the cofactor-binding domain, providing a visualization of how a chaperone assists in the sequestering of a precious cofactor inside an enzyme active site.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1419582112
