Intrinsically Disordered Protein

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Human CDK2 (blue) complex with cyclin-A (green) and P27 (pink) 1jsu: see p27kip1 below. P27 has undergone a disorder to order transition upon encountering these partners.

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References and Notes

  1. For the sake of brevity, this description is oversimplified. RNAse needed to be reduced to break disulfide bonds, as well as using 8 M urea, for denaturation. Oxidation without the denaturant then left an inactive enzyme because the disulfide bonds formed randomly, precluding proper folding except very slowly (many hours). Only when protein disulfide isomerase was added did the re-folding occur at a physiological rate (about a minute). The fact that RNAse could thus be trapped in an inactive conformation under physiological conditions contributed to the insights developed by Anfinsen and his team. Proteins lacking disulfides renatured in seconds. For details, see Anfinsen's Nobel Lecture.
  2. A similar observation was made around the same time by then graduate student Lisa Steiner in the lab of Fred Richards at Yale University. Neither Richards nor advisor Joseph Fruton thought the observation interesting enough to publish. It was an answer to a question not yet asked. This story is recounted by David Eisenberg, see the next citation.
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  5. Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z. Intrinsically disordered protein. J Mol Graph Model. 2001;19(1):26-59. PMID:11381529
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  8. Summary of the previous paper (Tompa, 2002): The disorder of intrinsically disordered proteins (IDP's) is crucial to their functions. They may adopt defined but extended structures when bound to cognate ligands. Their amino acid compositions are less hydrophobic than those of soluble proteins. They lack hydrophobic cores, and hence do not become insoluble when heated. About 40% of eukaryotic proteins have at least one long (>50 residues) disordered region. Roughly 10% of proteins in various genomes have been predicted to be fully disordered. Presently over 100 IDP's have been identified; none are enzymes. Obviously, IDP's are greatly underrepresented in the Protein Data Bank, although there are a few cases of an IDP bound to a folded (intrinsically structured) protein. Here, Tompa suggests five functional categories for intrinsically unstructured proteins and domains: entropic chains (bristles to ensure spacing, springs, flexible spacers/linkers), effectors (inhibitors and disassemblers), scavengers, assemblers, and display sites. (Summary by Eric Martz.)
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See Also


The bulk of this article was written by Tzviya Zeev-Ben-Mordehai. Contributions by Eric Martz were minor -- his name is listed first due to a technicality.

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