{"doi":"10.1101/2022.03.11.483825","title":"Oligomer-to-Monomer Transition Underlies the Chaperone Function of AAGAB in AP1/AP2 Assembly","abstract":"Abstract Assembly of protein complexes is facilitated by assembly chaperones. Alpha and gamma adaptin binding protein (AAGAB) is a chaperone governing the assembly of the heterotetrameric adaptor complexes 1 and 2 (AP1 and AP2) involved in clathrin-mediated membrane trafficking. Here, we found that before AP1/2 binding, AAGAB exists as a homotetramer. AAGAB tetramerization is mediated by its C-terminal domain, which is critical for AAGAB stability and is missing in mutant proteins found in patients with the skin disease punctate palmoplantar keratoderma type 1 (PPKP1). We solved the crystal structure of the tetramerization domain (TD), revealing a dimer of dimer assembly. Interestingly, AAGAB uses the same TD to recognize and stabilize the γ subunit in the AP1 complex and the α subunit in the AP2 complex, forming binary complexes containing only one copy of AAGAB. These findings demonstrate a dual role of TD in stabilizing resting AAGAB and binding to substrates, providing a molecular explanation for disease-causing AAGAB mutations. The oligomerization state transition mechanism may also underlie the functions of other assembly chaperones.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306657,"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":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":719454,"name":"Ishara Datta","orcid":"0000-0002-4493-5487","position":1,"is_corresponding":false},{"id":719453,"name":"Rui Yang","orcid":"0000-0002-9311-1265","position":2,"is_corresponding":false},{"id":274722,"name":"Chun Wan","orcid":"0000-0002-8827-0552","position":3,"is_corresponding":false},{"id":285502,"name":"Bing Wang","orcid":"0000-0003-0431-8449","position":4,"is_corresponding":false},{"id":308880,"name":"Huan He","orcid":"0000-0002-5014-9124","position":5,"is_corresponding":false},{"id":404460,"name":"Suzhao Li","orcid":"0000-0001-8641-2759","position":6,"is_corresponding":false},{"id":274723,"name":"Jingshi Shen","orcid":"0000-0001-9595-1148","position":7,"is_corresponding":false},{"id":285505,"name":"Qian Yin","orcid":"0000-0002-8481-150X","position":8,"is_corresponding":false},{"id":1001061,"name":"Yuan Tian","orcid":"0000-0001-8828-1131","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:52.703737Z","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":[]}