title: Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains.
abstract: Recognition of ubiquitin and polyubiquitin chains by ubiquitin-binding domains (UBDs) is vital for ubiquitin-mediated signaling pathways. The endoplasmic reticulum resident RING finger ubiquitin ligase (E3) gp78 regulates critical proteins via the ubiquitin-proteasome system to maintain cellular homeostasis and includes a UBD known as the CUE domain, which is essential for function. A probable role of this domain is to recognize ubiquitin-modified substrates, enabling gp78 to assemble polyubiquitin chains on these substrates and mark them for degradation. Here, we report the molecular details of the interaction of gp78CUE domain with ubiquitin and diubiquitin. The gp78CUE domain exhibits a well-defined set of interactions with ubiquitin and a dynamic, promiscuous interaction with diubiquitin chains. This leads to a model in which the CUE domain functions to both facilitate substrate binding and enable switching between adjacent ubiquitin molecules of a growing chain to enable processivity in ubiquitination.
authors.affiliation: Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Chen
authors.forename: Jess
authors.initials: J
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Sergey
authors.initials: S
authors.lastname: Tarasov
authors.forename: Aaren
authors.initials: A
authors.lastname: King
authors.forename: Allan M
authors.initials: AM
authors.lastname: Weissman
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Byrd
authors.forename: Ranabir
authors.initials: R
authors.lastname: Das
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D025821:Polyubiquitin / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D060285:Receptors, Autocrine Motility Factor / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D025821:Polyubiquitin; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor