2NVU: Structure Of Appbp1-Uba3~nedd8-Nedd8-Mgatp-Ubc12(C111a), A Trapped Ubiquitin-Like Protein Activation Complex

Citation:
Abstract
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.
PDB ID: 2NVUDownload
MMDB ID: 44074
PDB Deposition Date: 2006/11/13
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2NVU: pentameric; determined by author
Molecular Components in 2NVU
Label Count Molecule
Proteins (5 molecules)
1
Nedd8-activating Enzyme E1 Regulatory Subunit(Gene symbol: NAE1)
Molecule annotation
1
Maltose Binding Protein/nedd8-activating Enzyme E1 Catalytic Subunit Chimera(Gene symbol: UBA3)
Molecule annotation
1
Nedd8-conjugating Enzyme Ubc12(Gene symbol: UBE2M)
Molecule annotation
2
Nedd8(Gene symbol: NEDD8)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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