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PDBsum entry 1bu9
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Hormone/growth factor
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PDB id
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1bu9
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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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Tumor suppressor ink4: determination of the solution structure of p18ink4c and demonstration of the functional significance of loops in p18ink4c and p16ink4a.
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Authors
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J.Li,
I.J.Byeon,
K.Ericson,
M.J.Poi,
P.O'Maille,
T.Selby,
M.D.Tsai.
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Ref.
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Biochemistry, 1999,
38,
2930-2940.
[DOI no: ]
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PubMed id
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Abstract
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Since the structures of several ankyrin-repeat proteins including the INK4
(inhibitor of cyclin-dependent kinase 4) family have been reported recently, the
detailed structures and the functional roles of the loops have drawn
considerable interest. This paper addresses the potential importance of the
loops of ankyrin-repeat proteins in three aspects. First, the solution structure
of p18INK4C was determined by NMR, and the loop structures were analyzed in
detail. The loops adapt nascent antiparallel beta-sheet structures, but the
positions are slightly different from those in the crystal structure. A detailed
comparison between the solution structures of p16 and p18 has also been
presented. The determination of the p18 solution structure made such detailed
comparisons possible for the first time. Second, the [1H,15N]HSQC NMR experiment
was used to probe the interactions between p18INK4C and other proteins. The
results suggest that p18INK4C interacts very weakly with dna K and glutathione
S-transferase via the loops. The third aspect employed site-specific mutagenesis
and functional assays. Three mutants of p18 and 11 mutants of p16 were
constructed to test functional importance of loops and helices. The results
suggest that loop 2 is likely to be part of the recognition surface of p18INK4C
or p16INK4A for CDK4, and they provide quantitative functional contributions of
specific residues. Overall, our results enhance understanding of the structural
and functional roles of the loops in INK4 tumor suppressors in particular and in
ankyrin-repeat proteins in general.
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