Structure of the ubr-box of the UBR1 ubiquitin ligase
Publication Abstract from PubMed
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.
Structural basis of substrate recognition and specificity in the N-end rule pathway.,Matta-Camacho E, Kozlov G, Li FF, Gehring K Nat Struct Mol Biol. 2010 Oct;17(10):1182-7. Epub 2010 Sep 12. PMID:20835242
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.