{"doi":"10.1101/2023.08.24.554671","title":"Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast","abstract":"The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":410830,"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":0.9516,"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":1081122,"name":"Huan Jin","orcid":"0000-0001-5886-7481","position":1,"is_corresponding":false},{"id":1145640,"name":"Thomas G. Reidy","orcid":null,"position":2,"is_corresponding":false},{"id":1145228,"name":"Brandon Palomino-Alonso","orcid":"0009-0005-5125-8858","position":3,"is_corresponding":false},{"id":1145229,"name":"Christopher J. Zysnarski","orcid":"0000-0002-1474-9499","position":4,"is_corresponding":false},{"id":969293,"name":"Fatima Javed","orcid":"0000-0002-5939-8039","position":5,"is_corresponding":false},{"id":416668,"name":"Sagar Lahiri","orcid":"0000-0002-9563-6188","position":6,"is_corresponding":false},{"id":416669,"name":"Mara C. Duncan","orcid":"0000-0002-2383-0109","position":7,"is_corresponding":false},{"id":991244,"name":"Lucas J. Marmorale","orcid":"0000-0001-8926-4368","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:21:38.940853Z","pmid":"37662263","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":[]}