{"doi":"10.1101/2020.10.08.332312","title":"Structure and mechanism of TRAPPIII-mediated Rab1 activation","abstract":"ABSTRACT The GTPase Rab1 is a master regulator of both the early secretory pathway and autophagy. Rab1 activation is controlled by its GEF (guanine nucleotide exchange factor), the multi-subunit TRAPPIII complex. The Trs85 regulatory subunit is critical for robust activation of Rab1 but its mechanistic role within the complex has remained unclear. Here we report the cryo-EM structure of the intact yeast TRAPPIII complex bound to its substrate Rab1/Ypt1. The orientation of the Rab1/Ypt1 hypervariable domain when bound to the complex leads to a model for how TRAPPIII associates with and activates Rab1/Ypt1 at the membrane surface. We identify a conserved amphipathic α-helix motif within Trs85 and demonstrate that this helix is required for stable membrane binding and Rab1/Ypt1 activation by TRAPPIII. Taken together, our results provide a comprehensive analysis of the structure and function of the yeast TRAPPIII complex and reveal that the key function of Trs85 is to serve as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125454,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9407,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":277860,"name":"Ben P. Phillips","orcid":"0000-0001-9117-4695","position":1,"is_corresponding":false},{"id":571516,"name":"Kumar Yugandhar","orcid":"0000-0003-1141-4439","position":2,"is_corresponding":false},{"id":481578,"name":"Ethan J. Sanford","orcid":"0000-0003-0722-3058","position":3,"is_corresponding":false},{"id":248967,"name":"Marcus B. Smolka","orcid":"0000-0001-9952-2885","position":4,"is_corresponding":false},{"id":268021,"name":"Haiyuan Yu","orcid":"0000-0001-7597-6049","position":5,"is_corresponding":false},{"id":277864,"name":"Elizabeth A. Miller","orcid":"0000-0002-1033-8369","position":6,"is_corresponding":false},{"id":277256,"name":"J. Christopher Fromme","orcid":"0000-0002-8837-0473","position":7,"is_corresponding":false},{"id":571515,"name":"Aaron M.N. Joiner","orcid":"0000-0001-9049-2384","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-18T23:15:15.482227Z","pmid":null,"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":[]}