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PDBsum entry 1ldj
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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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Structure of the cul1-Rbx1-Skp1-F boxskp2 scf ubiquitin ligase complex.
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Authors
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N.Zheng,
B.A.Schulman,
L.Song,
J.J.Miller,
P.D.Jeffrey,
P.Wang,
C.Chu,
D.M.Koepp,
S.J.Elledge,
M.Pagano,
R.C.Conaway,
J.W.Conaway,
J.W.Harper,
N.P.Pavletich.
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Ref.
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Nature, 2002,
416,
703-709.
[DOI no: ]
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PubMed id
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Abstract
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SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate
the ubiquitination of diverse regulatory and signalling proteins. Here we
present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which
shows that Cul1 is an elongated protein that consists of a long stalk and a
globular domain. The globular domain binds the RING finger protein Rbx1 through
an intermolecular beta-sheet, forming a two-subunit catalytic core that recruits
the ubiquitin-conjugating enzyme. The long stalk, which consists of three
repeats of a novel five-helix motif, binds the Skp1-F boxSkp2 protein
substrate-recognition complex at its tip. Cul1 serves as a rigid scaffold that
organizes the Skp1-F boxSkp2 and Rbx1 subunits, holding them over 100 A apart.
The structure suggests that Cul1 may contribute to catalysis through the
positioning of the substrate and the ubiquitin-conjugating enzyme, and this
model is supported by Cul1 mutations designed to eliminate the rigidity of the
scaffold.
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Figure 1.
Figure 1: Overall structure of the Cul1-Rbx1-Skp1-F boxSkp2
quaternary complex. Cul1, Rbx1, Skp1 and the F-box of Skp2
are coloured in green, red, blue and magenta, respectively. The
five helices that make up the cullin-repeat motif are labelled
for the second repeat. Figures were prepared with the programs
MOLSCRIPT49, GL_RENDER and POVRAY (L. Essar, personal
communication).
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Figure 4.
Figure 4: Cul1-Skp1-F boxSkp2 interface and the putative
protein-binding site on other cullins. a, View of the
interface between Cul1 (dark green) and Skp1-F boxSkp2 (blue and
magenta) in an orientation rotated 90° about the vertical axis
of Fig. 1. The residues of Cul1, Skp1, and F-boxSkp2 that are
involved in the interactions are shown in light green, cyan and
pink colours, respectively. Hydrogen bonds are indicated by
white dotted lines. b, Sequence alignments of the orthologues of
Cul2, Cul3 and Cul5 in the regions that correspond to the Skp1-F
boxSkp2 binding site of Cul1. Invariant residues are highlighted
in yellow. Cul4B is not shown because only human and fly
sequences are available. The published Cul4A sequence lacks most
of the first cullin repeat. c, The sequence of Cul3 was mapped
onto the structure of the Cul1 NTD on the basis of sequence
homology, and the resulting model's surface was coloured
according to conservation in Cul3 orthologues. The model surface
shows that the residues identical in Cul3 orthologues (yellow)
cluster on the same surface region as the Skp1-F boxSkp2 binding
site of Cul1 (Fig. 2b). A Cul5 model constructed the same way
shows a similar feature.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2002,
416,
703-709)
copyright 2002.
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