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PDBsum entry 1p1a
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DNA binding protein
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PDB id
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1p1a
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Binding surface mapping of intra- And interdomain interactions among hhr23b, Ubiquitin, And polyubiquitin binding site 2 of s5a.
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Authors
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K.S.Ryu,
K.J.Lee,
S.H.Bae,
B.K.Kim,
K.A.Kim,
B.S.Choi.
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Ref.
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J Biol Chem, 2003,
278,
36621-36627.
[DOI no: ]
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PubMed id
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Abstract
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hHR23B is the human homologue of the yeast protein RAD23 and is known to
participate in DNA repair by stabilizing xeroderma pigmentosum group C protein.
However, hHR23B and RAD23 also have many important functions related to general
proteolysis. hHR23B consists of N-terminal ubiquitin-like (UbL), ubiquitin
association 1 (UBA1), xeroderma pigmentosum group C binding, and UBA2 domains.
The UBA domains interact with ubiquitin (Ub) and inhibit the assembly of
polyubiquitin. On the other hand, the UbL domain interacts with the poly-Ub
binding site 2 (PUbS2) domain of the S5a protein, which can carry
polyubiquitinated substrates into the proteasome. We calculated the NMR
structure of the UbL domain of hHR23B and determined binding surfaces of UbL and
Ub to UBA1, UBA2, of hHR23B and PUbS2 of S5a by using chemical shift
perturbation. Interestingly, the surfaces of UbL and Ub that bind to UBA1, UBA2,
and PUbS2 are similar, consisting of five beta-strands and their connecting
loops. This is the first report that an intramolecular interaction between UbL
and UBA domains is possible, and this interaction could be important for the
control of proteolysis by hHR23B. The binding specificities of UbL and Ub for
PUbS1, PUbS2, and general ubiquitin-interacting motifs, which share the LALA
motif, were evaluated. The UBA domains bind to the surface of Ub including
Lys-48, which is required for multiubiquitin assembly, possibly explaining the
observed inhibition of multiubiquitination by hHR23B. The UBA domains bind to
UbL through electrostatic interactions supported by hydrophobic interactions and
to Ub mainly through hydrophobic interactions supported by electrostatic
interactions.
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Figure 1.
FIG. 1. Structure of the UbL domain in hHR23B derived from
NMR experiments. Left, the 14 calculated structures were
superimposed as a stereo view. Right, the ribbon diagram of one
selected structure obtained with the MOLMOL program shows five
 -strands, one long  -helix
and one turn of -helix, and one short
3[10] helix.
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Figure 3.
FIG. 3. Surface potential maps and surface mapping of
chemical shift perturbations. Electrostatic potential maps were
overlaid on the molecular surface of all domains of hHR23B and
Ub with a cutoff value of 10 kT/e. The molecules of (i) UbL and
Ub and (ii) UBA1 and UBA2 were matched to have the same
surfaces, respectively. The amount of chemical shift
perturbation was represented by using the following different
colors: violet red, red, orange red, orange, and yellow,
respectively, from high to low perturbation residues. The boxed
figure is the model structure of -helical region of
PUbS2 from S5a.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
36621-36627)
copyright 2003.
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