title: A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases.
abstract: How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. Here we address how the RING E3 RBX1 positions NEDD8's E2 (UBC12) and substrate (CUL1). We find that existing structures are incompatible with CUL1 NEDD8ylation and report a new conformation of RBX1 that places UBC12 adjacent to CUL1. We propose RING domain rotation as a general mechanism for UBL transfer for the largest family of E3s.
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. matthew.calabrese@stjude.org
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Calabrese
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Scott
authors.forename: David M
authors.initials: DM
authors.lastname: Duda
authors.forename: Christy R R
authors.initials: CR
authors.lastname: Grace
authors.forename: Igor
authors.initials: I
authors.lastname: Kurinov
authors.forename: Richard W
authors.initials: RW
authors.lastname: Kriwacki
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Schulman
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D044842:Cullin Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D000075687:NEDD8 Protein; D017434:Protein Structure, Tertiary; D044786:S-Phase Kinase-Associated Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry*; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C486317:CAND1 protein, human; C496871:CUL5 protein, human; D002352:Carrier Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C479529:RBX1 protein, human; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C112595:UBC12 protein, S cerevisiae; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; C485632:HRT1 protein, S cerevisiae; D044843:SKP Cullin F-Box Protein Ligases