title: The linkage specificity determination of Ube2g2-gp78 mediated polyubiquitination.
abstract: Polyubiquitin chain linkage specificity or topology is essential for its role in diverse cellular processes. Previous studies pay more attentions to the linkage specificity of the first ubiquitin moieties, whereas, little is known about the editing mechanism of linkage specificity in longer polyubiquitin chains. gp78 and its cognate E2-Ube2g2 catalyze lysine48 (K48)-linked polyubiquitin chains to promote the degradation of targeted proteins. Here, we show that the linkage specificity of the entire polyubiquitin chain is determined by the conjugation manner of the first ubiquitin molecule but not the following ones. Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains.
authors.affiliation: The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Gao
authors.affiliation: The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address: liuwx@ioz.ac.cn.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China. Electronic address: leways@ioz.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D004789:Enzyme Activation; D025821:Polyubiquitin / Q000138:chemical synthesis*; D011485:Protein Binding; D060285:Receptors, Autocrine Motility Factor / Q000737:chemistry*; D013329:Structure-Activity Relationship; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry*
chemical_list: D025821:Polyubiquitin; C471617:UBE2G2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor
keywords: CUE; Linkage specificity; Polyubiquitin chain; gp78