{"doi":"10.1083/jcb.202407105","title":"The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux","abstract":"During autophagy, toxic cargo is encapsulated by autophagosomes and trafficked to lysosomes for degradation. NBR1, an autophagy receptor targeting ubiquitinated aggregates, serves as a model for studying the multivalent, heterotypic interactions of cargo-bound receptors. Here, we find that three critical NBR1 partners-ATG8-family proteins, FIP200, and TAX1BP1-each bind to distinct, overlapping determinants within a short linear interaction motif (SLiM). To explore whether overlapping SLiMs extend beyond NBR1, we analyzed >100 LC3-interacting regions (LIRs), revealing that FIP200 and/or TAX1BP1 binding to LIRs is a common phenomenon and suggesting LIRs as protein interaction hotspots. Phosphomimetic peptides demonstrate that phosphorylation generally enhances FIP200 and ATG8-family binding but not TAX1BP1, indicating differential regulation. In vivo, LIR-mediated interactions with TAX1BP1 promote optimal NBR1 flux by leveraging additional functionalities from TAX1BP1. These findings reveal a one-to-many binding modality in the LIR motif of NBR1, illustrating the cooperative mechanisms of autophagy receptors and the regulatory potential of multifunctional SLiMs.","journal":"The Journal of Cell Biology","year":2025,"id":519026,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"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":273951,"name":"Amelia E Ohnstad","orcid":"0009-0006-2358-6202","position":1,"is_corresponding":false},{"id":448663,"name":"Michael J. Ragusa","orcid":"0000-0002-0231-0876","position":2,"is_corresponding":false},{"id":273957,"name":"Christopher J. Shoemaker","orcid":"0000-0003-2004-6340","position":3,"is_corresponding":false},{"id":273953,"name":"Brian J. North","orcid":"0000-0003-0463-7028","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"39928048","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":[]}