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High resolution structure of the HDGF PWWP domain: A potential DNA binding domain
Author(s) -
Lukasik Stephen M.,
Cierpicki Tomasz,
Borloz Matthew,
Grembecka Jolanta,
Everett Allen,
Bushweller John H.
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.051751706
Subject(s) - chemistry , chromatin , dna binding domain , dna , microbiology and biotechnology , biophysics , transcription factor , biochemistry , biology , gene
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.