3NY2: Structure Of The Ubr-Box Of Ubr2 Ubiquitin Ligase

Citation:
Abstract
The N-end rule links the half-life of a protein to the identity of its N-terminal residue. Destabilizing N-terminal residues are recognized by E3 ubiquitin ligases, termed N-recognins. A conserved structural domain called the UBR box is responsible for their specificity. Here we report the crystal structures of the UBR boxes of the human N-recognins UBR1 and UBR2, alone and in complex with an N-end rule peptide, Arg-Ile-Phe-Ser. These structures show that the UBR box adopts a previously undescribed fold stabilized through the binding of three zinc ions to form a binding pocket for type 1 N-degrons. NMR experiments reveal a preference for N-terminal arginine. Peptide binding is abrogated by N-terminal acetylation of the peptide or loss of the positive charge of the N-terminal residue. These results rationalize and refine the empirical rules for the classification of type 1 N-degrons. We also confirm that a missense mutation in UBR1 that is responsible for Johanson-Blizzard syndrome leads to UBR box unfolding and loss of function.
PDB ID: 3NY2Download
MMDB ID: 84049
PDB Deposition Date: 2010/7/14
Updated in MMDB: 2010/10
Experimental Method:
x-ray diffraction
Resolution: 2.61  Å
Source Organism:
Similar Structures:
Biological Unit for 3NY2: monomeric; determined by author and by software (PISA)
Molecular Components in 3NY2
Label Count Molecule
Protein (1 molecule)
1
E3 Ubiquitin-protein Ligase Ubr2(Gene symbol: UBR2)
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

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