HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: ps.051751706v1 15/2/314    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lukasik, S. M. Articles by Bushweller, J. H. Search for Related Content PubMed PubMed Citation Articles by Lukasik, S. M. Articles by Bushweller, J. H. Social Bookmarking                   What's this?

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

¹ Department of Chemistry and ² Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA
³ Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA

(RECEIVED August 3, 2005; FINAL REVISION November 3, 2005; ACCEPTED November 7, 2005)

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, J-couplings, 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.

Keywords: HDGF; PWWP; growth factor; heart development; dipolar couplings; protein structure/folding; protein–nucleic acid interactions; DNA-binding domains; structure; structural proteins; NMR spectroscopy; heteronuclear NMR

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.051751706.

Reprint requests to: John H. Bushweller, Department of Chemistry and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22906, USA; e-mail: jhb4v{at}virginia.edu; fax: (434) 982-1616.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M.-C. Shun, Y. Botbol, X. Li, F. Di Nunzio, J. E. Daigle, N. Yan, J. Lieberman, M. Lavigne, and A. Engelman Identification and Characterization of PWWP Domain Residues Critical for LEDGF/p75 Chromatin Binding and Human Immunodeficiency Virus Type 1 Infectivity J. Virol., December 1, 2008; 82(23): 11555 - 11567. [Abstract] [Full Text] [PDF]

				T. A. Brown-Bryan, L. S. Leoh, V. Ganapathy, F. J. Pacheco, M. Mediavilla-Varela, M. Filippova, T. A. Linkhart, R. Gijsbers, Z. Debyser, and C. A. Casiano Alternative Splicing and Caspase-Mediated Cleavage Generate Antagonistic Variants of the Stress Oncoprotein LEDGF/p75 Mol. Cancer Res., August 1, 2008; 6(8): 1293 - 1307. [Abstract] [Full Text] [PDF]

				C. Marchand, K. Krajewski, H.-F. Lee, S. Antony, A. A. Johnson, R. Amin, P. Roller, M. Kvaratskhelia, and Y. Pommier Covalent binding of the natural antimicrobial peptide indolicidin to DNA abasic sites Nucleic Acids Res., October 6, 2006; (2006) gkl667v3. [Abstract] [Full Text] [PDF]