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PDBsum entry 1a12
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Guanine nucleotide exchange factor
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PDB id
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1a12
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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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The 1.7 a crystal structure of the regulator of chromosome condensation (rcc1) reveals a seven-Bladed propeller.
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Authors
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L.Renault,
N.Nassar,
I.Vetter,
J.Becker,
C.Klebe,
M.Roth,
A.Wittinghofer.
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Ref.
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Nature, 1998,
392,
97.
[DOI no: ]
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PubMed id
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Abstract
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The gene encoding the regulator of chromosome condensation (RCC1) was cloned by
virtue of its ability to complement the temperature-sensitive phenotype of the
hamster cell line tsBN2, which undergoes premature chromosome condensation or
arrest in the G1 phase of the cell cycle at non-permissive temperatures. RCC1
homologues have been identified in many eukaryotes, including budding and
fission yeast. Mutations in the gene affect pre-messenger RNA processing and
transport, mating, initiation of mitosis and chromatin decondensation,
suggesting that RCC1 is important in the control of nucleo-cytoplasmic transport
and the cell cycle. Biochemically, RCC1 is a guanine-nucleotide-exchange factor
for the nuclear Ras homologue Ran; it increases the dissociation of Ran-bound
GDP by 10(5)-fold. It may also bind to DNAvia a protein-protein complex. Here we
show that the structure of human RCC1, solved to 1.7-A resolution by X-ray
crystallography, consists of a seven-bladed propeller formed from internal
repeats of 51-68 residues per blade. The sequence and structure of the repeats
differ from those of WD40-domain proteins, which also form seven-bladed
propellers and include the beta-subunits of G proteins. The nature of the
structure explains the consequences of a wide range of known mutations. The
region of the protein that is involved in guanine-nucleotide exchange is located
opposite the region that is thought to be involved in chromosome binding.
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Figure 1.
Figure 1 Overall three-dimensional structure of RCC1. Ribbon
diagram of the RCC1 propeller structure as viewed along (a) or
perpendicular to (b) the central shaft. The blades (a) are
numbered (B1-B7) along the sequence. Semiconserved histidines
that connect the blades and invariant residues believed to be
important for the interaction with Ran are shown as
ball-and-stick representations.
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Figure 2.
Figure 2 Primary- and secondary-structure alignment. Sequence
alignment, obtained using the GCG program (adjusted manually) of
five RCC1 homologues (from top to bottom: human, hamster,
Drosophila, Schizosaccharomyces pombe and Saccharomyces
cerevisiae) and the protein product, RPGR/RP3 of the X-linked
retinitis pigmentosa gene, along with the secondary structure of
human RCC1. The seven blades are coloured as in Fig. 1. Residues
highly conserved in seven RCC1 homologues (including Xenopus and
Caenorhabditis albicans RCC1) are boxed; invariant residues are
also shown in bold. The structurally conserved residues among
different repeats of RCC1 and RPGR/RP3 are shaded brown. Alanine
mutations that perturb the GEF activity14 are shown in blue
(human); the mutation responsible for the tsBN2 (refs 1, 2)
phenotype is shown in pink (hamster); and RCC1 mutations in S.
cerevisiae and S. pombe^3-7,13 are shown in red. Asterisks
indicate truncated sequences.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
392,
97-0)
copyright 1998.
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