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

Stephen M. Lukasik, Tomasz Cierpicki, Matthew Borloz, Jolanta Grembecka, Allen D 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 2006

Fingerprint

DNA
Chromatin Assembly and Disassembly
Nuclear magnetic resonance
Titration
Chromatin
Amino Acid Motifs
Ports and harbors
Mitogens
hepatoma-derived growth factor
Assays
Proteins
Genes
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lukasik, S. M., Cierpicki, T., Borloz, M., Grembecka, J., Everett, A. D., & 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

High resolution structure of the HDGF PWWP domain : A potential DNA binding domain. / Lukasik, Stephen M.; Cierpicki, Tomasz; Borloz, Matthew; Grembecka, Jolanta; Everett, Allen D; Bushweller, John H.

In: Protein Science, Vol. 15, No. 2, 02.2006, p. 314-323.

Research output: Contribution to journalArticle

Lukasik, SM, Cierpicki, T, Borloz, M, Grembecka, J, Everett, AD & Bushweller, JH 2006, 'High resolution structure of the HDGF PWWP domain: A potential DNA binding domain', Protein Science, vol. 15, no. 2, pp. 314-323. https://doi.org/10.1110/ps.051751706
Lukasik, Stephen M. ; Cierpicki, Tomasz ; Borloz, Matthew ; Grembecka, Jolanta ; Everett, Allen D ; Bushweller, John H. / High resolution structure of the HDGF PWWP domain : A potential DNA binding domain. In: Protein Science. 2006 ; Vol. 15, No. 2. pp. 314-323.
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