{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kruse T"],"funding":["Wellcome Trust","NIGMS NIH HHS"],"pagination":["eadp5491"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11446282"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(40)"],"pubmed_abstract":["The PP2A-B55 phosphatase regulates a plethora of signaling pathways throughout eukaryotes. How PP2A-B55 selects its substrates presents a severe knowledge gap. By integrating AlphaFold modeling with comprehensive high-resolution mutational scanning, we show that α helices in substrates bind B55 through an evolutionary conserved mechanism. Despite a large diversity in sequence and composition, these α helices share key amino acid determinants that engage discrete hydrophobic and electrostatic patches. Using deep learning protein design, we generate a specific and potent competitive peptide inhibitor of PP2A-B55 substrate interactions. With this inhibitor, we uncover that PP2A-B55 regulates the nuclear exosome targeting (NEXT) complex by binding to an α-helical recruitment module in the RNA "],"journal":["Science advances"],"pubmed_title":["Substrate recognition principles for the PP2A-B55 protein phosphatase."],"pmcid":["PMC11446282"],"funding_grant_id":["R35 GM119455"],"pubmed_authors":["Jensen TH","Varga JK","Hein JB","Mendez BL","Benavides-Puy I","Nilsson J","Jeyaprakash AA","Sotelo-Parrilla P","Kettenbach AN","Chan CB","Garland W","Weisser MB","Schueler-Furman O","Kruse T","McEwan BC","Garvanska DH"],"additional_accession":[]},"is_claimable":false,"name":"Substrate recognition principles for the PP2A-B55 protein phosphatase.","description":"The PP2A-B55 phosphatase regulates a plethora of signaling pathways throughout eukaryotes. How PP2A-B55 selects its substrates presents a severe knowledge gap. By integrating AlphaFold modeling with comprehensive high-resolution mutational scanning, we show that α helices in substrates bind B55 through an evolutionary conserved mechanism. Despite a large diversity in sequence and composition, these α helices share key amino acid determinants that engage discrete hydrophobic and electrostatic patches. Using deep learning protein design, we generate a specific and potent competitive peptide inhibitor of PP2A-B55 substrate interactions. With this inhibitor, we uncover that PP2A-B55 regulates the nuclear exosome targeting (NEXT) complex by binding to an α-helical recruitment module in the RNA ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-18T15:57:14.96Z","creation":"2025-04-07T02:52:53.03Z"},"accession":"S-EPMC11446282","cross_references":{"pubmed":["39356758"],"doi":["10.1126/sciadv.adp5491"]}}