{"doi":"10.1101/2021.02.05.429362","title":"Caprin-1 binding to the critical stress granule protein G3BP1 is regulated by pH","abstract":"Abstract G3BP is the central hub within the protein-RNA interaction network of stress-induced bio-molecular condensates known as stress granules (SG). The SG-associated proteins Caprin-1 and USP10 exhibit mutually exclusive binding to the structured NTF2-domain of G3BP1, thereby regulating G3BP1-mediated condensation, but with opposite effects: Caprin-1 promotes but USP10 inhibits SG formation. Herein, we present the crystal structure of G3BP1-NTF2 in complex with a Caprin-1 derived short linear motif (SLiM), which provides a molecular understanding for the mutually exclusive binding of USP10 and Caprin-1 to G3BP1. Caprin-1 but not USP10 contacts two G3BP1-NTF2 histidine residues, which was confirmed using biochemical, biophysical and cellular biological binding assays. G3BP1/Caprin-1 interactions disrupted via point mutations resulted in fewer and smaller SG condensates. In addition, biochemical binding assays demonstrated reduced binding of Caprin-1 to G3BP1 at lower pH values. Finally, ratiometric pH sensitive measurements of SGs revealed a substantial drop in pH compared to the adjacent cytosol, suggesting that reduced pH can fine-tune and regulate the G3BP1-mediated interaction network via a NTF2-mediated pH-sensitive SLiM-selection mechanism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215009,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":809226,"name":"Marc D. Panas","orcid":"0000-0002-7373-0341","position":1,"is_corresponding":false},{"id":431252,"name":"Lucy Williams","orcid":null,"position":2,"is_corresponding":false},{"id":108000,"name":"Nancy Kedersha","orcid":"0000-0002-8363-9816","position":3,"is_corresponding":false},{"id":40551,"name":"Jonas Simon Fleck","orcid":"0000-0002-4686-7254","position":4,"is_corresponding":false},{"id":552629,"name":"Timothy J.C. Tan","orcid":"0000-0001-5337-5357","position":5,"is_corresponding":false},{"id":809227,"name":"Anders Olsson","orcid":"0000-0003-2508-3968","position":6,"is_corresponding":false},{"id":563632,"name":"Ainhoa Moliner Morro","orcid":"0000-0001-8963-3063","position":7,"is_corresponding":false},{"id":559059,"name":"Leo Hanke","orcid":"0000-0001-5514-2418","position":8,"is_corresponding":false},{"id":809228,"name":"Johan Nilvebrant","orcid":"0000-0002-6104-6446","position":9,"is_corresponding":false},{"id":809229,"name":"Kim Anh Giang","orcid":"0000-0002-7097-9408","position":10,"is_corresponding":false},{"id":809230,"name":"Per‐Åke Nygren","orcid":"0000-0003-4214-6991","position":11,"is_corresponding":false},{"id":35039,"name":" Paul Anderson","orcid":"0000-0001-5349-281X","position":12,"is_corresponding":false},{"id":424999,"name":"Adnane Achour","orcid":"0000-0003-0432-710X","position":13,"is_corresponding":false},{"id":559064,"name":"Gerald M. McInerney","orcid":"0000-0003-2257-7241","position":14,"is_corresponding":false},{"id":809225,"name":"Tim Schulte","orcid":"0000-0002-7322-8933","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:51.201033Z","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":[]}