title: Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1.
abstract: Fas-associated factor (FAF)-1 is a multidomain protein that was first identified as a member of the Fas death-inducing signaling complex, but later found to be involved in various biological processes. Although the exact mechanisms are not clear, FAF1 seems to play an important role in cancer, asbestos-induced mesotheliomas, and Parkinson's disease. It interacts with polyubiquitinated proteins, Hsp70, and p97/VCP (valosin-containing protein), in addition to the proteins of the Fas-signaling pathway. We have determined the crystal structure of the ubiquitin-associated domain of human FAF1 (hFAF1-UBA) and examined its interaction with ubiquitin and ubiquitin-like proteins using nuclear magnetic resonance. hFAF1-UBA revealed a canonical three-helical bundle that selectively binds to mono- and di-ubiquitin (Lys48-linked), but not to SUMO-1 (small ubiquitin-related modifier 1) or NEDD8 (neural precursor cell expressed, developmentally down-regulated 8). The interaction between hFAF1-UBA and di-ubiquitin involves hydrophobic interaction accompanied by a transition in the di-ubiquitin conformation. These results provide structural insight into the mechanism of polyubiquitin recognition by hFAF1-UBA.
authors.affiliation: Magnetic Resonance Team, Korea Basic Science Institute, 804-1 Yangchung-Ri, Ochang, Chungbuk, Korea.
authors.forename: Jinsue
authors.initials: J
authors.lastname: Song
authors.forename: Joon Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Kyoung-Seok
authors.initials: KS
authors.lastname: Ryu
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Jeon
authors.forename: Eunice Eunkyeong
authors.initials: EE
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics*; D016415:Sequence Alignment; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C490780:FAF1 protein, human; C109184:UBD protein, human; D025801:Ubiquitin; D014452:Ubiquitins