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spinqualitylabelsall models 2fzp, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the USP8 interaction domain of human NRDP1

Overview

Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated, targets such as epidermal growth factor receptors and is involved in, clathrin-mediated internalization. In 1182 residues, USP8 contains, multiple domains, including coiled-coil, rhodanese, and catalytic domains., We report the first high-resolution crystal structures of these domains, and discuss their implications for USP8 function. The amino-terminal, domain is a homodimer with a novel fold. It is composed of two five-helix, bundles, where the first helices are swapped, and carboxyl-terminal, helices are extended in an antiparallel fashion. The structure of the, rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals, the canonical rhodanese fold but with a distorted primordial active site., The USP8 recognition domain of NRDP1 has a novel protein fold that, interacts with a conserved peptide loop of the rhodanese domain. A, consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the, carboxyl-terminal catalytic domain of USP8 exhibits the conserved, tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon, subdomain near the ubiquitin binding site further suggests a, polyubiquitin-specific binding site and a mechanism for substrate induced, conformational changes.

About this Structure

2FZP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8)., Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S, J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239

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