Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone
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...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/98024 https://orcid.org/0000-0001-5486-2755 |
| _version_ | 1826200991565873152 |
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| author | Jost, Marco Cracan, Valentin Hubbard, Paul A. Banerjee, Ruma Drennan, Catherine L |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Jost, Marco Cracan, Valentin Hubbard, Paul A. Banerjee, Ruma Drennan, Catherine L |
| author_sort | Jost, Marco |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:44:57Z |
| format | Article |
| id | mit-1721.1/98024 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:44:57Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/980242022-10-01T05:42:37Z Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone Jost, Marco Cracan, Valentin Hubbard, Paul A. Banerjee, Ruma Drennan, Catherine L Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Jost, Marco Hubbard, Paul A. Drennan, Catherine L. 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. National Institutes of Health (U.S.) (Grant GM069857) Massachusetts Institute of Technology. Poitras Pre-Doctoral Fellowship 2015-08-05T13:41:00Z 2015-08-05T13:41:00Z 2015-02 2014-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/98024 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. https://orcid.org/0000-0001-5486-2755 en_US http://dx.doi.org/10.1073/pnas.1419582112 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Jost, Marco Cracan, Valentin Hubbard, Paul A. Banerjee, Ruma Drennan, Catherine L Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title | Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title_full | Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title_fullStr | Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title_full_unstemmed | Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title_short | Visualization of a radical B[subscript 12] enzyme with its G-protein chaperone |
| title_sort | visualization of a radical b subscript 12 enzyme with its g protein chaperone |
| url | http://hdl.handle.net/1721.1/98024 https://orcid.org/0000-0001-5486-2755 |
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