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http://purl.uniprot.org/citations/32910895http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32910895http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32910895http://www.w3.org/2000/01/rdf-schema#comment"Membrane protein biogenesis faces the challenge of chaperoning hydrophobic transmembrane helices for faithful membrane insertion. The guided entry of tail-anchored proteins (GET) pathway targets and inserts tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane with an insertase (yeast Get1/Get2 or mammalian WRB/CAML) that captures the TA from a cytoplasmic chaperone (Get3 or TRC40, respectively). Here, we present cryo-electron microscopy reconstructions, native mass spectrometry, and structure-based mutagenesis of human WRB/CAML/TRC40 and yeast Get1/Get2/Get3 complexes. Get3 binding to the membrane insertase supports heterotetramer formation, and phosphatidylinositol binding at the heterotetramer interface stabilizes the insertase for efficient TA insertion in vivo. We identify a Get2/CAML cytoplasmic helix that forms a "gating" interaction with Get3/TRC40 important for TA insertion. Structural homology with YidC and the ER membrane protein complex (EMC) implicates an evolutionarily conserved insertion mechanism for divergent substrates utilizing a hydrophilic groove. Thus, we provide a detailed structural and mechanistic framework to understand TA membrane insertion."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.org/dc/terms/identifier"doi:10.1016/j.molcel.2020.08.012"xsd:string
http://purl.uniprot.org/citations/32910895http://purl.org/dc/terms/identifier"doi:10.1016/j.molcel.2020.08.012"xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Robinson C.V."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Robinson C.V."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Wu D."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Wu D."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Bolla J.R."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Bolla J.R."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Fiorentino F."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Fiorentino F."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Wild K."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Wild K."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Flemming D."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Flemming D."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Sinning I."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Sinning I."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Mehmood S."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Mehmood S."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Schmid V."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Schmid V."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Farkas A."xsd:string
http://purl.uniprot.org/citations/32910895http://purl.uniprot.org/core/author"Farkas A."xsd:string