{"doi":"10.1101/2023.03.23.533963","title":"Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B <sub>12</sub> delivery and repair","abstract":"Abstract G-proteins function as molecular switches to power cofactor translocation and confer fidelity in metal trafficking. MMAA, a G-protein motor, together with MMAB, an adenosyltransferase, orchestrate cofactor delivery and repair of B 12 -dependent human methylmalonyl-CoA mutase (MMUT). The mechanism by which the motor assembles and moves a &gt;1300 Da cargo, or fails in disease, are poorly understood. Herein, we report the crystal structure of the human MMUT-MMAA nanomotor assembly, which reveals a dramatic 180° rotation of the B 12 domain, exposing it to solvent. The nanomotor complex, stabilized by MMAA wedging between two MMUT domains, leads to ordering of the switch I and III loops, revealing the molecular basis of mutase-dependent GTPase activation. The structure explains the biochemical penalties incurred by methylmalonic aciduria-causing mutations that reside at the newly identified MMAA-MMUT interfaces.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":403959,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":495543,"name":"Markus Ruetz","orcid":"0000-0001-9540-7310","position":1,"is_corresponding":false},{"id":767314,"name":"Harsha Gouda","orcid":"0000-0003-4511-5875","position":2,"is_corresponding":false},{"id":1074318,"name":"Natalie Heitman","orcid":null,"position":3,"is_corresponding":false},{"id":960038,"name":"Madeline Yaw","orcid":null,"position":4,"is_corresponding":false},{"id":265994,"name":"Ruma Banerjee","orcid":"0000-0001-8332-3275","position":5,"is_corresponding":false},{"id":495542,"name":"Romila Mascarenhas","orcid":"0000-0002-5099-3528","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:40.264741Z","pmid":"36993209","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}