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

David S Libich1, Martin Schwalbe, Sachin Kate

  • 1Centre for Structural Biology, Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand. d.s.libich@massey.ac.nz

The FEBS Journal
|June 4, 2009
PubMed

Insights

Prostate apoptosis response factor-4 (Par-4) is a tumor-suppressive protein that is intrinsically disordered. Biophysical studies reveal Par-4 self-associates via its C-terminal domain, forming a coiled-coil structure crucial for its function.

Area of Science:

  • Molecular Biology
  • Protein Biochemistry
  • Cell Biology

Background:

  • Prostate apoptosis response factor-4 (Par-4) is a key tumor suppressor.
  • Par-4 regulates cell death and survival pathways.
  • It possesses a conserved coiled-coil region involved in binding interactions.

Purpose of the Study:

  • To investigate the structural and biophysical properties of Par-4.
  • To understand the role of intrinsic disorder in Par-4 function.
  • To elucidate the mechanism of Par-4 self-association.

Main Methods:

  • Bioinformatic analysis of Par-4 sequence.
  • Biophysical characterization including CD and NMR spectroscopy.
  • Proteolytic susceptibility and hydrodynamic radius measurements.
  • Urea-induced denaturation studies.

Main Results:

  • Par-4 is predominantly an intrinsically disordered protein.
  • Bioinformatics revealed low sequence complexity and polar/charged amino acid enrichment.
  • High proteolytic susceptibility and hydrodynamic radius indicate an extended structure.
  • Par-4 self-associates intramolecularly via its C-terminal domain to form a coiled-coil.
  • Disruption of self-association by urea leads to loss of secondary structure.

Conclusions:

  • Par-4's intrinsic disorder is a key feature of its structure.
  • Intramolecular association stabilizes the coiled-coil motif under physiological conditions.
  • Understanding Par-4 structure provides insights into its tumor-suppressive functions.

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