title: The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
abstract: The endosomal sorting complexes required for transport (ESCRTs) facilitate endosomal sorting of ubiquitinated cargo, MVB biogenesis, late stages of cytokinesis, and retroviral budding. Here we show that ubiquitin associated protein 1 (UBAP1), a subunit of human ESCRT-I, coassembles in a stable 1:1:1:1 complex with Vps23/TSG101, VPS28, and VPS37. The X-ray crystal structure of the C-terminal region of UBAP1 reveals a domain that we describe as a solenoid of overlapping UBAs (SOUBA). NMR analysis shows that each of the three rigidly arranged overlapping UBAs making up the SOUBA interact with ubiquitin. We demonstrate that UBAP1-containing ESCRT-I is essential for degradation of antiviral cell-surface proteins, such as tetherin (BST-2/CD317), by viral countermeasures, namely, the HIV-1 accessory protein Vpu and the Kaposi sarcoma-associated herpesvirus (KSHV) ubiquitin ligase K5.
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Agromayor
authors.forename: Nicolas
authors.initials: N
authors.lastname: Soler
authors.forename: Anna
authors.initials: A
authors.lastname: Caballe
authors.forename: Tonya
authors.initials: T
authors.lastname: Kueck
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Freund
authors.forename: Mark D
authors.initials: MD
authors.lastname: Allen
authors.forename: Mark
authors.initials: M
authors.lastname: Bycroft
authors.forename: Olga
authors.initials: O
authors.lastname: Perisic
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.forename: Bethan
authors.initials: B
authors.lastname: McDonald
authors.forename: Hartmut
authors.initials: H
authors.lastname: Scheel
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Stuart J D
authors.initials: SJ
authors.lastname: Neil
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Serrano
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D017874:Immediate-Early Proteins; D025801:Ubiquitin; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C405867:K5 protein, Human herpesvirus 8; C469867:UBAP1 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins