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http://purl.uniprot.org/citations/34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34523144http://www.w3.org/2000/01/rdf-schema#comment"Permeabilization of the outer mitochondrial membrane by pore-forming Bcl2 proteins is a crucial step for the induction of apoptosis. Despite a large set of data suggesting global conformational changes within pro-apoptotic Bak during pore formation, high-resolution structural details in a membrane environment remain sparse. Here, we used NMR and HDX-MS (Hydrogen deuterium exchange mass spectrometry) in lipid nanodiscs to gain important high-resolution structural insights into the conformational changes of Bak at the membrane that are dependent on a direct activation by BH3-only proteins. Furthermore, we determined the first high-resolution structure of the Bak transmembrane helix. Upon activation, α-helix 1 in the soluble domain of Bak dissociates from the protein and adopts an unfolded and dynamic potentially membrane-bound state. In line with this finding, comparative protein folding experiments with Bak and anti-apoptotic BclxL suggest that α-helix 1 in Bak is a metastable structural element contributing to its pro-apoptotic features. Consequently, mutagenesis experiments aimed at stabilizing α-helix 1 yielded Bak variants with delayed pore-forming activity. These insights will contribute to a better mechanistic understanding of Bak-mediated membrane permeabilization."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.org/dc/terms/identifier"doi:10.15252/embj.2020107159"xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/author"Hagn F."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/author"Haslbeck M."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/author"Schiller A."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/author"Ruhrnossl F."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/author"Sperl L.E."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/name"EMBO J"xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/pages"e107159"xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/title"High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane."xsd:string
http://purl.uniprot.org/citations/34523144http://purl.uniprot.org/core/volume"40"xsd:string
http://purl.uniprot.org/citations/34523144http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34523144
http://purl.uniprot.org/citations/34523144http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34523144
http://purl.uniprot.org/uniprot/#_A0A1L4AQQ4-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A0S2Z319-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_P10415-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_Q07817-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A0S2Z391-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A0S2Z3C5-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A0S2Z3D2-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A1L4AQQ5-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A1L4AQQ8-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144
http://purl.uniprot.org/uniprot/#_A0A1L4AQR6-mappedCitation-34523144http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523144