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PDBsum entry 1yfq
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Signaling protein
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PDB id
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1yfq
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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 1.1-Angstrom structure of the spindle checkpoint protein bub3p reveals functional regions.
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Authors
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D.K.Wilson,
D.Cerna,
E.Chew.
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Ref.
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J Biol Chem, 2005,
280,
13944-13951.
[DOI no: ]
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PubMed id
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Abstract
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Bub3p is a protein that mediates the spindle checkpoint, a signaling pathway
that ensures correct chromosome segregation in organisms ranging from yeast to
mammals. It is known to function by co-localizing at least two other proteins,
Mad3p and the protein kinase Bub1p, to the kinetochore of chromosomes that are
not properly attached to mitotic spindles, ultimately resulting in cell cycle
arrest. Prior sequence analysis suggested that Bub3p was composed of three or
four WD repeats (also known as WD40 and beta-transducin repeats), short sequence
motifs appearing in clusters of 4-16 found in many hundreds of eukaryotic
proteins that fold into four-stranded blade-like sheets. We have determined the
crystal structure of Bub3p from Saccharomyces cerevisiae at 1.1 angstrom and a
crystallographic R-factor of 15.3%, revealing seven authentic repeats. In light
of this, it appears that many of these repeats therefore remain hidden in
sequences of other proteins. Analysis of random and site-directed mutants
identifies the surface of Bub3p involved in checkpoint function through binding
of Bub1p and Mad3p. Sequence alignments indicate that these surfaces are mostly
conserved across Bub3 proteins from diverse species. A structural comparison
with other proteins containing WD repeats suggests that these folds may bind
partner proteins using similar surface areas on the top and sides of the
propeller. The sequences composing these regions are the most divergent within
the repeat across all WD repeat proteins and could potentially be modulated to
provide specificity in partner protein binding without perturbation of the core
structure.
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Figure 4.
FIG. 4. Conservation of protein binding surfaces in known
structures of WD repeat proteins complexed with partner
proteins. Functional surfaces of the WD repeat proteins G  and p40
indicate regions involved in partner protein binding and are
similar to the Bub3p surface shown in Fig. 2, A and B. All
models have an orientation similar to Fig. 1. Interaction
surfaces: A, G  binding to G (35); B,
phosducin binding to G (33); C, p16 binding to
p40 (27); D, p20 binding to p40 (27) are shown in red. These
figures were prepared using the program GRASP (45).
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Figure 6.
FIG. 6. Sequence alignments of Bub3 from various species.
scBUB3, S. cerevisiae; hsBUB3, human; mmBUB3, mouse; xlBUB3, X.
laevis; dmBUB3, Drosophila. Secondary structural elements are
identified based on the yeast structure. Residues that are
conserved among Bub3 homologs and shown in Fig. 2, B and C are
shaded gray. Locations of mutants failing to rescue the
BUB3-null mutant in this study are indicated by arrows.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
13944-13951)
copyright 2005.
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