{"doi":"10.1016/j.jbc.2022.102776","title":"Surface electrostatics dictate RNA-binding protein CAPRIN1 condensate concentration and hydrodynamic properties","abstract":"Biomolecular condensates concentrate proteins, nucleic acids, and small molecules and play an essential role in many biological processes. Their formation is tuned by a balance between energetically favorable and unfavorable contacts, with charge–charge interactions playing a central role in some systems. The positively charged intrinsically disordered carboxy-terminal region of the RNA-binding protein CAPRIN1 is one such example, phase separating upon addition of negatively charged ATP or high concentrations of sodium chloride (NaCl). Using solution NMR spectroscopy, we measured residue-specific near-surface electrostatic potentials (ϕENS) of CAPRIN1 along its NaCl-induced phase separation trajectory to compare with those obtained using ATP. In both cases, electrostatic shielding decreases ϕENS values, yet surface potentials of CAPRIN1 in the two condensates can be different, depending on the amount of NaCl or ATP added. Our results establish that even small differences in ϕENS can significantly affect the level of protein enrichment and the mechanical properties of the condensed phase, leading, potentially, to the regulation of biological processes. Biomolecular condensates concentrate proteins, nucleic acids, and small molecules and play an essential role in many biological processes. Their formation is tuned by a balance between energetically favorable and unfavorable contacts, with charge–charge interactions playing a central role in some systems. The positively charged intrinsically disordered carboxy-terminal region of the RNA-binding protein CAPRIN1 is one such example, phase separating upon addition of negatively charged ATP or high concentrations of sodium chloride (NaCl). Using solution NMR spectroscopy, we measured residue-specific near-surface electrostatic potentials (ϕENS) of CAPRIN1 along its NaCl-induced phase separation trajectory to compare with those obtained using ATP. In both cases, electrostatic shielding decreases ϕENS values, yet surface potentials of CAPRIN1 in the two condensates can be different, depending on the amount of NaCl or ATP added. Our results establish that even small differences in ϕENS can significantly affect the level of protein enrichment and the mechanical properties of the condensed phase, leading, potentially, to the regulation of biological processes. The phase separation of biomolecules controls many aspects of cellular function (1Hyman A.A. Weber C.A. Jülicher F. Liquid-liquid phase separation in biology.Annu. Rev. Cell Dev. Biol. 2014; 30: 39-58Crossref PubMed Scopus (1664) Google Scholar, 2Banani S.F. Lee H.O. Hyman A.A. Rosen M.K. Biomolecular condensates: organizers of cellular biochemistry.Nat. Rev. Mol. Cell Biol. 2017; 18: 285-298Crossref PubMed Scopus (2593) Google Scholar), and understanding the atomic details of the driving forces underlying this process has, therefore, been the subject of considerable efforts. The interactions that regulate the formation and disassembly of biological condensates have been extensively characterized via biochemical and computational studies (2Banani S.F. Lee H.O. Hyman A.A. Rosen M.K. Biomolecular condensates: organizers of cellular biochemistry.Nat. Rev. Mol. Cell Biol. 2017; 18: 285-298Crossref PubMed Scopus (2593) Google Scholar, 3Wang J. Choi J.-M. Holehouse A.S. Lee H.O. Zhang X. Jahnel M. et al.A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins.Cell. 2018; 174: 688-699.e16Abstract Full Text Full Text PDF PubMed Scopus (893) Google Scholar, 4Martin E.W. Holehouse A.S. Peran I. Farag M. Incicco J.J. Bremer A. et al.Valence and patterning of aromatic residues determine the phase behavior of prion-like domains.Science. 2020; 367: 694-699Crossref PubMed Scopus (380) Google Scholar); however, site-specific experimental information is lacking. Among the various interactions, the role of electrostatics is of particular interest as phase-separating proteins can be enriched in charged r","journal":"Journal of Biological Chemistry","year":2022,"id":252218,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":259597,"name":"Atul Rangadurai","orcid":"0000-0003-2019-313X","position":1,"is_corresponding":false},{"id":257869,"name":"Julie D. Forman‐Kay","orcid":"0000-0001-8265-972X","position":2,"is_corresponding":false},{"id":633086,"name":"Lewis E. Kay","orcid":"0000-0002-4054-4083","position":3,"is_corresponding":false},{"id":633085,"name":"Yuki Toyama","orcid":"0000-0003-0457-678X","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36496075","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":[]}