{"doi":"10.1016/j.str.2025.11.003","title":"Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved peptide motif","abstract":"Inherited mutations in VPS35 and LRRK2 kinase lead to hyperphosphorylation of Rab GTPases. RH2 domain-containing proteins from the RILP homology family, such as RILPL1, are Rab effectors that recognize the LRRK2-phosphorylated switch 2 threonine of phospho-Rab8A and phospho-Rab10. Phospho-Rabs are also seen on lysosomal membranes in complex with RILPL1 and TMEM55B, a 284-residue lysosomal membrane protein lacking homology to known proteins. Here, we report crystal structures of the cytosolic region 80–166 of TMEM55B alone and in complex with a C-terminal RILPL1 peptide, which we define as the TMEM55B-binding motif (TBM). The RILPL1 TBM sits in a shallow groove across two tandem RING-like domains of TMEM55B, each forming a Zn 2+ -stabilized 40-residue β-sandwich. Co-immunoprecipitation and mass spectrometry studies indicate that TMEM55B forms complexes independently of phospho-Rabs with conserved TBMs found in JIP3, JIP4, OCRL, WDR81, and TBC1D9B. These studies suggest that TMEM55B acts as a central hub for adaptor recruitment on lysosomes.","journal":"Structure","year":2025,"id":549065,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":285686,"name":"Prosenjit Pal","orcid":"0000-0001-6848-4863","position":1,"is_corresponding":false},{"id":371637,"name":"Raja Sekhar Nirujogi","orcid":"0000-0002-3177-8566","position":2,"is_corresponding":false},{"id":1443224,"name":"Melanie Cavin","orcid":null,"position":3,"is_corresponding":false},{"id":1443225,"name":"Jaijeet Singh","orcid":null,"position":4,"is_corresponding":false},{"id":285688,"name":"Dario R. Alessi","orcid":"0000-0002-2140-9185","position":5,"is_corresponding":false},{"id":285689,"name":"Amir R. Khan","orcid":"0000-0003-1176-6952","position":6,"is_corresponding":false},{"id":285684,"name":"Dieter Waschbüsch","orcid":"0000-0002-8953-2585","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41314214","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":[]}