High resolution structure of the HDGF PWWP domain: A potential DNA binding domain

Stephen M. Lukasik, Tomasz Cierpicki, Matthew Borloz, Jolanta Grembecka, Allen Everett, John H. Bushweller

Research output: Contribution to journalArticle

Abstract

Hepatoma Derived Growth Factor (HDGF) is an endogenous nuclear-targeted mitogen that is linked with human disease. HDGF is a member of the weakly conserved PWWP domain family. This 70-amino acid motif, originally identified from the WHSC1 gene, has been found in more than 60 eukaryotic proteins. In addition to the PWWP domain, many proteins in this class contain known chromatin remodeling domains, suggesting a role for HDGF in chromatin remodeling. We have determined the NMR structure of the HDGF PWWP domain to high resolution using a combination of NOEs, Jcouplings, and dipolar couplings. Comparison of this structure to a previously determined structure of the HDGF PWWP domain shows a significant difference in the C-terminal region. Comparison to structures of other PWWP domains shows a high degree of similarity to the PWWP domain structures from Dnmt3b and mHRP. The results of selected and amplified binding assay and NMR titrations with DNA suggest that the HDGF PWWP domain may function as a nonspecific DNA-binding domain. Based on the NMR titrations, we propose a model of the interaction of the PWWP domain with DNA. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)314-323
Number of pages10
JournalProtein Science
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • DNA-binding domains
  • Dipolar couplings
  • Growth factor
  • HDGF
  • Heart development
  • Heteronuclear NMR
  • NMR spectroscopy
  • PWWP
  • Protein structure/folding
  • Protein-nucleic acid interactions
  • Structural proteins
  • Structure

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Lukasik, S. M., Cierpicki, T., Borloz, M., Grembecka, J., Everett, A., & Bushweller, J. H. (2006). High resolution structure of the HDGF PWWP domain: A potential DNA binding domain. Protein Science, 15(2), 314-323. https://doi.org/10.1110/ps.051751706