ArticleThe Journal of biological chemistry2013
Autoinhibition and signaling by the switch II motif in the G-protein chaperone of a radical B12 enzyme.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Cobalt-Sulfur Coordination Chemistry Drives BJournal of the American Chemical Society · 2023Article
- Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for BNature communications · 2023Article
- Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme BProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The human BMethods in enzymology · 2022Article
- Redox-Linked Coordination Chemistry Directs Vitamin BAccounts of chemical research · 2021Article
- Mechanistic Insights into the Metal-Dependent Activation of ZnInorganic chemistry · 2019Article
- Allosteric Regulation of Oligomerization by a BCell chemical biology · 2019Article
- Switch I-dependent allosteric signaling in a G-protein chaperone-BThe Journal of biological chemistry · 2017Article
- Metallochaperones and metalloregulation in bacteria.Essays in biochemistry · 2017Review
- Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical BThe Journal of biological chemistry · 2017Article
- Crystal structures of Mycobacterial MeaB and MMAA-like GTPases.Journal of structural and functional genomics · 2015Article
- Visualization of a radical B12 enzyme with its G-protein chaperone.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
MeaB is an accessory GTPase protein involved in the assembly, protection, and reactivation of 5'-deoxyadenosyl cobalamin-dependent methylmalonyl-CoA mutase (MCM). Mutations in the human ortholog of MeaB result in methylmalonic aciduria, an inborn error of metabolism. G-proteins typically utilize conserved switch I and II motifs for signaling to effector proteins via conformational changes elicited by nucleotide binding and hydrolysis. Our recent discovery that MeaB utilizes an unusual switch III region for bidirectional signaling with MCM raised questions about the roles of the switch I and II motifs in MeaB. In this study, we addressed the functions of conserved switch II residues by performing alanine-scanning mutagenesis. Our results demonstrate that the GTPase activity of MeaB is autoinhibited by switch II and that this loop is important for coupling nucleotide-sensitive conformational changes in switch III to elicit the multiple chaperone functions of MeaB. Furthermore, we report the structure of MeaB·GDP crystallized in the presence of AlFx(-) to form the putative transition state analog, GDP·AlF4(-). The resulting crystal structure and its comparison with related G-proteins support the conclusion that the catalytic site of MeaB is incomplete in the absence of the GTPase-activating protein MCM and therefore unable to stabilize the transition state analog. Favoring an inactive conformation in the absence of the client MCM protein might represent a strategy for suppressing the intrinsic GTPase activity of MeaB in which the switch II loop plays an important role.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.