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PDBsum entry 5tda
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References listed in PDB file
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Key reference
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Title
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Bound waters mediate binding of diverse substrates to a ubiquitin ligase.
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Authors
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J.Muñoz-Escobar,
E.Matta-Camacho,
C.Cho,
G.Kozlov,
K.Gehring.
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Ref.
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Structure, 2017,
25,
719.
[DOI no: ]
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PubMed id
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Abstract
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The N-end rule pathway controls the half-life of proteins based on their
N-terminal residue. Positively charged type 1 N-degrons are recognized by a
negatively charged pocket on the Zn finger named the UBR box. Here, we show that
the UBR box is rigid, but bound water molecules in the pocket provide the
structural plasticity required to bind different positively charged amino acids.
Ultra-high-resolution crystal structures of arginine, histidine, and methylated
arginine reveal that water molecules mediate the binding of N-degron peptides.
Using a high-throughput binding assay and isothermal titration calorimetry, we
demonstrate that the UBR box is able to bind methylated arginine and lysine
peptides with high affinity and measure the preference for hydrophobic residues
in the second position in the N-degron peptide. Finally, we show that the V122L
mutation present in Johanson-Blizzard syndrome patients changes the specificity
for the second position due to occlusion of the secondary pocket.
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Secondary reference #1
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Title
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Crystal structure of the ubr-Box domain of ubr2 in co with rlws n-Degron
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Authors
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J.Munoz-Escobar,
G.Kozlov,
E.P.Matta-Camacho,
K.Gehring.
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Ref.
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TO BE PUBLISHED ...
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