2nvu

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spinqualitylabelsall models PDB ID 2nvu Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.80Å
Ligands:	, and
Gene:	APPBP1 (Homo sapiens), UBE1C, UBA3 (Homo sapiens), UBE2M, UBC12 (Homo sapiens), NEDD8 (Homo sapiens)
Coordinates:	save as pdb, mmCIF, xml

Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex

Overview

Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades.

About this Structure

2NVU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity., Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA, Nature. 2007 Jan 25;445(7126):394-8. Epub 2007 Jan 14. PMID:17220875

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