5h7r

Structural basis of the flanking zinc-finger motifs crucial for the E3 ligase activity of the LNX1 RING domain

spinqualitylabelsall models 5h7r, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5h7r is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LNX1_HUMAN E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65 (By similarity). Isoform 2 provides an endocytic scaffold for IGSF5/JAM4 (By similarity). Publication Abstract from PubMed LNX1 (Ligand of Numb Protein-X 1) 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. Structure of LNX1:Ubc13~Ubiquitin complex reveals the role of additional motifs for the E3 ligase activity of LNX1.,Nayak D, Sivaraman J J Mol Biol. 2018 Feb 26. pii: S0022-2836(18)30089-5. doi:, 10.1016/j.jmb.2018.02.016. PMID:29496391 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures

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