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

被引：53

作者：

Lukasik, SM

Cierpicki, T

Borloz, M

Grembecka, J

Everett, A

Bushweller, JH ^{[1
]}

机构：

[1] Univ Virginia, Dept Chem, Charlottesville, VA 22906 USA

[2] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22906 USA

[3] Johns Hopkins Univ, Sch Med, Div Pediat Cardiol, Baltimore, MD 21287 USA

来源：

PROTEIN SCIENCE | 2006年 / 15卷 / 02期

关键词：

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;

D O I：

10.1110/ps.051751706

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：314 / 323

页数：10