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http://purl.uniprot.org/citations/22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22496420http://www.w3.org/2000/01/rdf-schema#comment"The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef directs virus escape from immune surveillance by subverting host cell intracellular signaling and membrane traffic to down-regulate cell-surface major histocompatibility complex class I (MHC-I). The interaction of Nef with the sorting proteins PACS-1 and PACS-2 mediates key signaling and trafficking steps required for Nef-mediated MHC-I down-regulation. Little is known, however, about the molecular basis underlying the Nef-PACS interaction. Here we identify the sites on Nef and the PACS proteins required for their interaction and describe the consequences of disrupting this interaction for Nef action. A previously unidentified cargo subsite on PACS-1 and PACS-2 interacted with a bipartite site on Nef formed by the EEEE(65) acidic cluster on the N-terminal domain and W(113) in the core domain. Mutation of these sites prevented the interaction between Nef and the PACS proteins on Rab5 (PACS-2 and PACS-1)- or Rab7 (PACS-1)-positive endosomes as determined by bimolecular fluorescence complementation and caused a Nef mutant defective in PACS binding to localize to distorted endosomal compartments. Consequently, disruption of the Nef-PACS interaction repressed Nef-induced MHC-I down-regulation in peripheral blood mononuclear cells. Our results provide insight into the molecular basis of Nef action and suggest new strategies to combat HIV-1."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.org/dc/terms/identifier"doi:10.1091/mbc.e11-11-0928"xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Thomas L."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Thomas G."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Dikeakos J.D."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Shinde U."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Elferich J."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/author"Kwon G."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/name"Mol Biol Cell"xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/pages"2184-2197"xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/title"An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I."xsd:string
http://purl.uniprot.org/citations/22496420http://purl.uniprot.org/core/volume"23"xsd:string
http://purl.uniprot.org/citations/22496420http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22496420
http://purl.uniprot.org/citations/22496420http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22496420
http://purl.uniprot.org/uniprot/#_P04601-mappedCitation-22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/#_Q8N7J0-mappedCitation-22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/#_Q8TDX4-mappedCitation-22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/#_Q8TDZ8-mappedCitation-22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/#_Q86VP3-mappedCitation-22496420http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/Q8TDX4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/P04601http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/Q86VP3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22496420
http://purl.uniprot.org/uniprot/Q8N7J0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22496420