Intrinsic disorder and coiled-coil formation in prostate apoptosis response factor 4

David S. Libich, Martin Schwalbe, Sachin Kate, Hariprasad Venugopal, Jolyon K. Claridge, Patrick J.B. Edwards, Kaushik Dutta, Steven M. Pascal

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Prostate apoptosis response factor-4 (Par-4) is an ubiquitously expressed pro-apoptotic and tumour suppressive protein that can both activate cell-death mechanisms and inhibit pro-survival factors. Par-4 contains a highly conserved coiled-coil region that serves as the primary recognition domain for a large number of binding partners. Par-4 is also tightly regulated by the aforementioned binding partners and by post-translational modifications. Biophysical data obtained in the present study indicate that Par-4 primarily comprises an intrinsically disordered protein. Bioinformatic analysis of the highly conserved Par-4 reveals low sequence complexity and enrichment in polar and charged amino acids. The high proteolytic susceptibility and an increased hydrodynamic radius are consistent with a largely extended structure in solution. Spectroscopic measurements using CD and NMR also reveal characteristic features of intrinsic disorder. Under physiological conditions, the data obtained show that Par-4 self-associates via the C-terminal domain, forming a coiled-coil. Interruption of self-association by urea also resulted in loss of secondary structure. These results are consistent with the stabilization of the coiled-coil motif through an intramolecular association.

Original languageEnglish (US)
Pages (from-to)3710-3728
Number of pages19
JournalFEBS Journal
Issue number14
StatePublished - Jul 2009
Externally publishedYes


  • Circular dichroism
  • Coiled-coil
  • Intrinsically disordered protein
  • Prostate apoptosis response factor 4
  • Solution NMR spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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