title: Structural regulation of cullin-RING ubiquitin ligase complexes.
abstract: Cullin-RING ligases (CRLs) compose the largest class of E3 ubiquitin ligases. CRLs are modular, multisubunit enzymes, comprising interchangeable substrate receptors dedicated to particular Cullin-RING catalytic cores. Recent structural studies have revealed numerous ways in which CRL E3 ligase activities are controlled, including multimodal E3 ligase activation by covalent attachment of the ubiquitin-like protein NEDD8, inhibition of CRL assembly/activity by CAND1, and several mechanisms of regulated substrate recruitment. These features highlight the potential for CRL activities to be tuned in responses to diverse cellular cues, and for modulating CRL functions through small-molecule agonists or antagonists. As the second installment of a two-review series, this article focuses on recent structural studies advancing our knowledge of how CRL activities are regulated.
authors.affiliation: Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Duda
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Scott
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Calabrese
authors.forename: Erik S
authors.initials: ES
authors.lastname: Zimmerman
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Schulman
mesh_terms: D000494:Allosteric Regulation; D003198:Computer Simulation; D044842:Cullin Proteins / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D044842:Cullin Proteins; D004791:Enzyme Inhibitors; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases