title: A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex.
abstract: HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-κB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between the Ub-like domain (UBL) of HOIL-1L and the Ub-associated domain (UBA) of HOIP. Our data indicate the functional significance of this non-canonical mode of UBA-UBL interaction in E3 complex formation and subsequent NF-κB activation. This study highlights the versatility and specificity of protein-protein interactions involving Ub/UBLs and their cognate proteins.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yagi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiromoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujita
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Uekusa
authors.forename: Maho
authors.initials: M
authors.lastname: Yagi-Utsumi
authors.forename: Eiji
authors.initials: E
authors.lastname: Kurimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Noda
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tokunaga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002942:Circular Dichroism; D006801:Humans; D047468:Immunoprecipitation; D009682:Magnetic Resonance Spectroscopy; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D020349:Surface Plasmon Resonance; D014157:Transcription Factors; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*; D014461:Ultracentrifugation
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D025801:Ubiquitin; C504507:RBCK1 protein, human; C558338:RNF31 protein, human; D044767:Ubiquitin-Protein Ligases