4IC3

Crystal structure of the F495L mutant XIAP RING domain

Summary for 4IC3

• Entry DOI: 10.2210/pdb4ic3/pdb
• Related: 4IC2
• Descriptor: E3 ubiquitin-protein ligase XIAP, ZINC ION, NICKEL (II) ION, ... (4 entities in total)
• Functional Keywords: ring domain, zinc-finger, e3 ligase, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 2
• Total formula weight: 17100.99

Authors

Nakatani, Y.,Day, C.L. (deposition date: 2012-12-09, release date: 2012-12-19, Last modification date: 2023-11-08)

Primary citation

Nakatani, Y.,Kleffmann, T.,Linke, K.,Condon, S.M.,Hinds, M.G.,Day, C.L.
Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase
Biochem.J., 450:629-638, 2013

PubMed Abstract: RING domains of E3 ligases promote transfer of Ub (ubiquitin) from the E2~Ub conjugate to target proteins. In many cases interaction of the E2~Ub conjugate with the RING domain requires its prior dimerization. Using cross-linking experiments we show that E2 conjugated ubiquitin contacts the RING homodimer interface of the IAP (inhibitor of apoptosis) proteins, XIAP (X-linked IAP) and cIAP (cellular IAP) 2. Structural and biochemical analysis of the XIAP RING dimer shows that an aromatic residue at the dimer interface is required for E2~Ub binding and Ub transfer. Mutation of the aromatic residue abolishes Ub transfer, but not interaction with Ub. This indicates that nuleophilic attack on the thioester bond depends on precise contacts between Ub and the RING domain. RING dimerization is a critical activating step for the cIAP proteins; however, our analysis shows that the RING domain of XIAP forms a stable dimer and its E3 ligase activity does not require an activation step.

PubMed: 23259674
DOI: 10.1042/BJ20121702

Experimental method

X-RAY DIFFRACTION (1.783 Å)