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PDBsum entry 1qb3
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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 and mutational analysis of the saccharomyces cerevisiae cell cycle regulatory protein cks1: implications for domain swapping, Anion binding and protein interactions.
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Authors
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Y.Bourne,
M.H.Watson,
A.S.Arvai,
S.L.Bernstein,
S.I.Reed,
J.A.Tainer.
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Ref.
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Structure, 2000,
8,
841-850.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The Saccharomyces cerevisiae protein Cks1 (cyclin-dependent kinase
subunit 1) is essential for cell-cycle progression. The biological function of
Cks1 can be modulated by a switch between two distinct molecular assemblies: the
single domain fold, which results from the closing of a beta-hinge motif, and
the intersubunit beta-strand interchanged dimer, which arises from the opening
of the beta-hinge motif. The crystal structure of a cyclin-dependent kinase
(Cdk) in complex with the human Cks homolog CksHs1 single-domain fold revealed
the importance of conserved hydrophobic residues and charged residues within the
beta-hinge motif. RESULTS: The 3.0 A resolution Cks1 structure reveals the
strict structural conservation of the Cks alpha/beta-core fold and the
beta-hinge motif. The beta hinge identified in the Cks1 structure includes a
novel pivot and exposes a cluster of conserved tyrosine residues that are
involved in Cdk binding but are sequestered in the beta-interchanged Cks homolog
suc1 dimer structure. This Cks1 structure confirms the conservation of the Cks
anion-binding site, which interacts with sidechain residues from the C-terminal
alpha helix of another subunit in the crystal. CONCLUSIONS: The Cks1 structure
exemplifies the conservation of the beta-interchanged dimer and the
anion-binding site in evolutionarily distant yeast and human Cks homologs.
Mutational analyses including in vivo rescue of CKS1 disruption support the dual
functional roles of the beta-hinge residue Glu94, which participates in Cdk
binding, and of the anion-binding pocket that is located 22 A away and on an
opposite face to Glu94. The Cks1 structure suggests a biological role for the
beta-interchanged dimer and the anion-binding site in targeting Cdks to specific
phosphoproteins during cell-cycle progression.
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Figure 4.
Figure 4. Cks1 anion-binding site and glutamine tail. (a)
Glu106 and Tyr107 residues (magenta bonds and polar atoms
colored spheres) within the C-terminal helix a3 (not present in
other Cks structures) bind to the five invariant residues
(Arg33, Arg42, Arg102, Ser82 and Trp85, orange bonds) forming
the anion-binding site located at the dimer interface of two
b-interchanged Cks1 dimers (yellow and blue subunits). In
addition, Arg111 in helix a3 stacks against Tyr30 in b1 (green
bonds in this interdimer interface). (b) Electron-density map
and model for the ordered position of the glutamine tail. Stereo
pair of the 3 Å resolution 2F[o]-F[c] electron-density maps,
contoured at 1.2s, showing the first four glutamine residues,
Gln118-Gln121, out of the 16 present in the Cks1 glutamine tail.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
841-850)
copyright 2000.
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