3NY3

Structure of the ubr-box of UBR2 in complex with N-degron

Summary for 3NY3

• Entry DOI: 10.2210/pdb3ny3/pdb
• Related: 3NY1 3NY2
• Descriptor: E3 ubiquitin-protein ligase UBR2, N-degron, ZINC ION, ... (4 entities in total)
• Functional Keywords: zinc finger-like, ubiquitin ligase, protein binding, lygase, ligase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (By similarity): Q8IWV8
• Total number of polymer chains: 2
• Total formula weight: 8956.20

Authors

Matta-Camacho, E.,Kozlov, G.,Li, F.,Gehring, K. (deposition date: 2010-07-14, release date: 2010-08-11, Last modification date: 2024-02-21)

Primary citation

Matta-Camacho, E.,Kozlov, G.,Li, F.F.,Gehring, K.
Structural basis of substrate recognition and specificity in the N-end rule pathway.
Nat.Struct.Mol.Biol., 17:1182-1187, 2010

PubMed 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.

PubMed: 20835242
DOI: 10.1038/nsmb.1894

Experimental method

X-RAY DIFFRACTION (1.6 Å)