Visualization of a radical B12 enzyme with its G-protein chaperone
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. In this paper, 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. Finally and 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.
- Authors:
-
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry
- Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Biological Chemistry
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry. Dept. of Biology. Howard Hughes Medical Inst.
- Publication Date:
- Research Org.:
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
- OSTI Identifier:
- 1171849
- Grant/Contract Number:
- AC02-06CH11357; AC02-05CH11231; GM069857; DK45776; P41 GM103403
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 112; Journal Issue: 8; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; metallocofactor delivery; vitamin B12; metallochaperone; G protein; crystallography
Citation Formats
Jost, Marco, Cracan, Valentin, Hubbard, Paul A., Banerjee, Ruma, and Drennan, Catherine L. Visualization of a radical B12 enzyme with its G-protein chaperone. United States: N. p., 2015.
Web. doi:10.1073/pnas.1419582112.
Jost, Marco, Cracan, Valentin, Hubbard, Paul A., Banerjee, Ruma, & Drennan, Catherine L. Visualization of a radical B12 enzyme with its G-protein chaperone. United States. https://doi.org/10.1073/pnas.1419582112
Jost, Marco, Cracan, Valentin, Hubbard, Paul A., Banerjee, Ruma, and Drennan, Catherine L. 2015.
"Visualization of a radical B12 enzyme with its G-protein chaperone". United States. https://doi.org/10.1073/pnas.1419582112. https://www.osti.gov/servlets/purl/1171849.
@article{osti_1171849,
title = {Visualization of a radical B12 enzyme with its G-protein chaperone},
author = {Jost, Marco and Cracan, Valentin and Hubbard, Paul A. and Banerjee, Ruma and Drennan, Catherine L.},
abstractNote = {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. In this paper, 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. Finally and 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.},
doi = {10.1073/pnas.1419582112},
url = {https://www.osti.gov/biblio/1171849},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 8,
volume = 112,
place = {United States},
year = {Mon Feb 09 00:00:00 EST 2015},
month = {Mon Feb 09 00:00:00 EST 2015}
}
Web of Science
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