5dka | pdb_00005dka

A C2HC zinc finger is essential for the activity of the RING ubiquitin ligase RNF125

spinqualitylabelsall models 5dka, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dka is a 2 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 1.55Å Ligands: CL, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease RN125_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Function RN125_HUMAN E3 ubiquitin-protein ligase that acts as a positive regulator of T-cell activation. E3 ligase proteins mediate ubiquitination and subsequent proteasomal degradation of target proteins. Publication Abstract from PubMed The activity of RING ubiquitin ligases (E3s) depends on an interaction between the RING domain and ubiquitin conjugating enzymes (E2), but posttranslational events or additional structural elements, yet largely undefined, are frequently required to enhance or regulate activity. Here, we show for the ubiquitin ligase RNF125 that, in addition to the RING domain, a C2HC Zn finger (ZnF) is crucial for activity, and a short linker sequence (Li2(120-128)) enhances activity. The contribution of these regions was first shown with truncated proteins, and the essential role of the ZnF was confirmed with mutations at the Zn chelating Cys residues. Using NMR, we established that the C2HC ZnF/Li2(120-128) region is crucial for binding of the RING domain to the E2 UbcH5a. The partial X-ray structure of RNF125 revealed the presence of extensive intramolecular interactions between the RING and C2HC ZnF. A mutation at one of the contact residues in the C2HC ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Thus, we identified the structural basis for an essential role of the C2HC ZnF and conclude that this domain stabilizes the RING domain, and is therefore required for binding of RNF125 to an E2. A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125.,Bijlmakers MJ, Teixeira JM, Boer R, Mayzel M, Puig-Sarries P, Karlsson G, Coll M, Pons M, Crosas B Sci Rep. 2016 Jul 14;6:29232. doi: 10.1038/srep29232. PMID:27411375 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures

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