Intrinsic structural disorder and sequence features of the cell cycle inhibitor p57Kip2.
The cell cycle inhibitor p57Kip2 induces cell cycle arrest by inhibiting the activity of cyclin-dependent kinases. p57, although active as a cyclin A-CDK2 inhibitor, is largely unfolded or intrinsically disordered as shown by circular dichroism and fluorescence spectra characteristic of an unfolded protein and a hydrodynamic radius consistent with an unfolded structure. In addition, the N-terminal domain of p57 is both functionally independent as a cyclin A-CDK2 inhibitor and unstructured, as demonstrated by circular dichroism and fluorescence spectra indicative of unfolded proteins, a lack of 1H chemical shift dispersion and a hydrodynamic radius consistent with a highly unfolded structure. The amino acid compositions of full-length p57 and the excised QT domain of p57 exhibit significant deviations from the average composition of globular proteins that are consistent with the observed intrinsic disorder. However, the amino acid composition of the CDK inhibition domain of p57 does not exhibit such a striking deviation from the average values observed for proteins, implying that a general low level of hydrophobicity, rather than depletion or enrichment in specific amino acids, contributes to the intrinsic disorder of the excised p57 CDK inhibition domain.
Adkins
Joshua N
JN
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA.
Lumb
Kevin J
KJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D002453:Cell Cycle; D002942:Circular Dichroism; D003001:Cloning, Molecular; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D018844:Cyclin-Dependent Kinases