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PDBsum entry 1ndd
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Signaling protein
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PDB id
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1ndd
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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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Crystal structure of the human ubiquitin-Like protein nedd8 and interactions with ubiquitin pathway enzymes.
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Authors
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F.G.Whitby,
G.Xia,
C.M.Pickart,
C.P.Hill.
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Ref.
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J Biol Chem, 1998,
273,
34983-34991.
[DOI no: ]
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PubMed id
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Abstract
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The NEDD8/Rub1 class of ubiquitin-like proteins has been implicated in
progression of the cell cycle from G1 into S phase. These molecules undergo a
metabolism that parallels that of ubiquitin and involves specific interactions
with many different proteins. We report here the crystal structure of
recombinant human NEDD8 refined at 1.6-A resolution to an R factor of 21.9%. As
expected from the high sequence similarity (57% identical), the NEDD8 structure
closely resembles that reported previously for ubiquitin. We also show that
recombinant human NEDD8 protein is activated, albeit inefficiently, by the
ubiquitin-activating (E1) enzyme and that NEDD8 can be transferred from E1 to
the ubiquitin conjugating enzyme E2-25K. E2-25K adds NEDD8 to a polyubiquitin
chain with an efficiency similar to that of ubiquitin. A chimeric tetramer
composed of three ubiquitins and one histidine-tagged NEDD8 binds to the 26 S
proteasome with an affinity similar to that of tetraubiquitin. Seven residues
that differ from the corresponding residues in ubiquitin, but are conserved
between NEDD8 orthologs, are candidates for mediating interactions with
NEDD8-specific partners. One such residue, Ala-72 (Arg in ubiquitin), is shown
to perform a key role in selecting against reaction with the ubiquitin E1
enzyme, thereby acting to prevent the inappropriate diversion of NEDD8 into
ubiquitin-specific pathways.
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Figure 3.
Fig. 3. Stereoview ribbon representation of NEDD8. N and
C termini are labeled N and C. Secondary structure was defined
with PROMOTIF (59). Helices are colored green: helix 1, residues
23-34; helix 2, 38-40; helix 3, 56-59. Helix 1 is type  , whereas
helices 2 and 3 are type 3[10]. According to the strict
definitions used by PROMOTIF, helix 2 does not occur in two of
the four NEDD8 molecules in the asymmetric unit, although the
conformations are close to those of standard helices.  strands are
colored red: strand 1, residues 2-6; strand 2, 12-16; strand 3,
41-45, strand 4, 48-49; strand 5, 66-71. Strand 1 has one extra
residue in one of the four molecules in the asymmetric unit.
Residues discussed in the text are shown explicitly.
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Figure 6.
Fig. 6. Space-filling representation of conserved and
divergent residues. Three views of NEDD8 are shown. The front
view is related to the orientation of Fig. 3 by a rotation about
the vertical axis of approximately 90° and a twist of
approximately 20°. Notice that the residues Glu-31, Glu-28,
and Arg-25, are labeled at the side of the front view and are in
the center of Fig. 3. The color code is the same as the text
background colors of Fig. 4; invariant residues are magenta,
conserved/divergent residues are yellow, and divergent residues
are blue. The C terminus is labeled with a C.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1998,
273,
34983-34991)
copyright 1998.
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