Two-state conformational equilibrium in the Par-4 leucine zipper domain

Martin Schwalbe, Kaushik Dutta, David S. Libich, Hariprasad Venugopal, Jolyon K. Claridge, David A. Gell, Joel P. Mackay, Patrick J.B. Edwards, Steven M. Pascal

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Prostate apoptosis response factor-4 (Par-4) is a pro-apoptotic and tumor-suppressive protein. A highly conserved heptad repeat sequence at the Par-4 C-terminus suggests the presence of a leucine zipper (LZ). This C-terminal region is essential for Par-4 self-association and interaction with various effector proteins. We have used nuclear magnetic resonance (NMR) spectroscopy to fully assign the chemical shift resonances of a peptide comprising the LZ domain of Par-4 at neutral pH. Further, we have investigated the properties of the Par-4 LZ domain and two point mutants under a variety of conditions using NMR, circular dichroism (CD), light scattering, and bioinformatics. Results indicate an environment-dependent conformational equilibrium between a partially ordered monomer (POM) and a predominantly coiled coil dimer (CCD). The combination of techniques used allows the time scales of the equilibrium to be probed and also helps to identify features of the amino acid sequence that may influence the equilibrium.

Original languageEnglish (US)
Pages (from-to)2433-2449
Number of pages17
JournalProteins: Structure, Function and Bioinformatics
Volume78
Issue number11
DOIs
StatePublished - Aug 15 2010

Keywords

  • Circular dichroism
  • Leucine zipper
  • Prostate apoptosis response factor 4
  • Solution NMR spectroscopy

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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