Entry PED2AAA: Unbound p27 KID domain

Entry summary

Random pool MD SAXS NMR Validated

Authors: Sivashankar G. Sivakolundu; Donald Bashford; Richard W. Kriwacki

Publication: Disordered p27Kip1 Exhibits Intrinsic Structure Resembling the Cdk2/Cyclin A-bound Conformation

Release date: 2014-01-16


p27Kip1 (p27) influences cell division by regulating nuclear cyclin- dependent kinases. Before binding, p27 is at least partially disordered and folds upon binding its Cdk/cyclin targets. 30-40% of human proteins, including p27, are predicted to contain disordered segments, and have been termed intrinsically unstructured proteins (IUPs). Unfortunately, the inherent dynamics of IUPs hamper detailed analysis of their structure/ function relationships. Here, we describe the use of molecular dynamics (MD) computations and solution NMR spectroscopy to reveal that several segments of the p27 kinase inhibitory domain (p27-KID), in addition to the previously characterized helical segment, exist as highly populated, intrinsically folded structural units (IFSUs). Several IFSUs resemble structural features of bound p27-KID, while another exhibits alternative conformations. Interestingly, the highly conserved, specificity determining segment of p27 is shown to be highly disordered. Elucidation of IFSUs within p27-KID allows consideration of their influences on the thermo- dynamics and kinetics of Cdk/cyclin binding. The degree to which IFSUs are populated within p27-KID is surprising and suggests that other putative IUPs contain IFSUs that may be studied using similar techniques.

Sample images

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Most compact conformation

Average conformation

Most extended conformation

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Protein information

p27 Kip1

Biological function: Cyclin-dependent protein serine/threonine kinase inhibitor activity [ref]

Protein name: p27 Kip1
UniProt link: O43806
Organism: Homo sapiens
Expressed in: Escherichia coli BL21 (DE3)
Number of residues: 69
Theoretic molecular weight: 8370.3
Theoretic isoelectric point: 5.16
Sequence range (relative to UniProt): 25-93
Post-translational modifications: No
Mutations: No

Amino acid sequence:


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