{"doi":"10.1073/pnas.2409139121","title":"Molecular insights into the interaction between a disordered protein and a folded RNA","abstract":"Intrinsically disordered protein regions (IDRs) are well established as contributors to intermolecular interactions and the formation of biomolecular condensates. In particular, RNA-binding proteins (RBPs) often harbor IDRs in addition to folded RNA-binding domains that contribute to RBP function. To understand the dynamic interactions of an IDR-RNA complex, we characterized the RNA-binding features of a small (68 residues), positively charged IDR-containing protein, Small ERDK-Rich Factor (SERF). At high concentrations, SERF and RNA undergo charge-driven associative phase separation to form a protein- and RNA-rich dense phase. A key advantage of this model system is that this threshold for demixing is sufficiently high that we could use solution-state biophysical methods to interrogate the stoichiometric complexes of SERF with RNA in the one-phase regime. Herein, we describe our comprehensive characterization of SERF alone and in complex with a small fragment of the HIV-1 Trans-Activation Response (TAR) RNA with complementary biophysical methods and molecular simulations. We find that this binding event is not accompanied by the acquisition of structure by either molecule; however, we see evidence for a modest global compaction of the SERF ensemble when bound to RNA. This behavior likely reflects attenuated charge repulsion within SERF via binding to the polyanionic RNA and provides a rationale for the higher-order assembly of SERF in the context of RNA. We envision that the SERF-RNA system will lower the barrier to accessing the details that support IDR-RNA interactions and likewise deepen our understanding of the role of IDR-RNA contacts in complex formation and liquid-liquid phase separation.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":441539,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":498778,"name":"Emery T. Usher","orcid":"0000-0002-8303-9992","position":1,"is_corresponding":false},{"id":1254599,"name":"Selin Dedeoğlu","orcid":"0009-0006-2697-8631","position":2,"is_corresponding":false},{"id":1254600,"name":"Matthew J. Crotteau","orcid":"0009-0004-9613-6777","position":3,"is_corresponding":false},{"id":1104848,"name":"Olivia A. Fraser","orcid":"0000-0001-9104-1921","position":4,"is_corresponding":false},{"id":274208,"name":"Neela H. Yennawar","orcid":"0000-0001-7278-659X","position":5,"is_corresponding":false},{"id":369044,"name":"Varun V. Gadkari","orcid":"0000-0001-6145-3773","position":6,"is_corresponding":false},{"id":369045,"name":"Brandon T. Ruotolo","orcid":"0000-0002-6084-2328","position":7,"is_corresponding":false},{"id":107330,"name":"Alex S. Holehouse","orcid":"0000-0002-4155-5729","position":8,"is_corresponding":false},{"id":613813,"name":"Loïc Salmon","orcid":"0000-0002-0249-6279","position":9,"is_corresponding":false},{"id":498779,"name":"Scott A. Showalter","orcid":"0000-0001-5179-032X","position":10,"is_corresponding":false},{"id":919800,"name":"James C.A. Bardwell","orcid":"0000-0003-1683-1944","position":11,"is_corresponding":false},{"id":1051068,"name":"Rishav Mitra","orcid":"0000-0002-8898-7289","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:11.152920Z","pmid":"39589885","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":[]}