5H7R

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

Summary for 5H7R

• Entry DOI: 10.2210/pdb5h7r/pdb
• Related: 5H7S
• Descriptor: E3 ubiquitin-protein ligase LNX, ZINC ION (3 entities in total)
• Functional Keywords: ring, ubiquitination, e3 ligase, zn finger motif, ligase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q8TBB1
• Total number of polymer chains: 1
• Total formula weight: 14887.57

Authors

Nayak, D.,Sivaraman, J. (deposition date: 2016-11-21, release date: 2017-11-29, Last modification date: 2023-11-08)

Primary citation

Nayak, D.,Sivaraman, J.
Structure of LNX1:Ubc13~Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1.
J. Mol. Biol., 430:1173-1188, 2018

PubMed Abstract: 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.

PubMed: 29496391
DOI: 10.1016/j.jmb.2018.02.016

Experimental method

X-RAY DIFFRACTION (1.7 Å)