Structure of LNX1:Ubc13 ~ Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1
Copyright policy )Structure of LNX1:Ubc13 ~ Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1
LNX1 (ligand of numb protein-X1) is a RING and PDZ domain-containing E3 ubiquitin ligase that ubiquitinates human c-Src kinase. Here, we report the identification and structure of the ubiquitination domain of LNX1, the identification of Ubc13/Ube2V2 as a functional E2 in vitro, and the structural and functional studies of the Ubc13~Ub intermediate in complex with the ubiquitination domain of LNX1. The RING domain of LNX1 is embedded between two zinc-finger motifs (Zn-RING-Zn), both of which are crucial for its ubiquitination activity. In the heterodimeric complex, the ubiquitin of one monomer shares more buried surface area with LNX1 of the other monomer and these interactions are unique and essential for catalysis. This study reveals how the LNX1 RING domain is structurally and mechanistically dependent on other motifs for its E3 ligase activity, and describes how dimeric LNX1 recruits ubiquitin-loaded Ubc13 for Ub transfer via E3 ligase-mediated catalysis.
- National University of Singapore Singapore
Models, Molecular, Binding Sites, Protein Conformation, Ubiquitin-Protein Ligases, Amino Acid Motifs, Ubiquitination, Zinc Fingers, Catalysis, Ubiquitin-Conjugating Enzymes, Humans, Protein Multimerization, RING Finger Domains, Protein Binding
Models, Molecular, Binding Sites, Protein Conformation, Ubiquitin-Protein Ligases, Amino Acid Motifs, Ubiquitination, Zinc Fingers, Catalysis, Ubiquitin-Conjugating Enzymes, Humans, Protein Multimerization, RING Finger Domains, Protein Binding
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