Home LiteratureArticle Details
PMID: 16384999 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Protein science : a publication of the Protein Society ·Vol. 15 ·No. 2 ·2006-02-00 ·Pages 314-23

Lukasik SM, Cierpicki T, Borloz M, Grembecka J, Everett A, Bushweller JH

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, 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.

MeSH Terms
Base Sequence Binding Sites DNA/metabolism Histidine/genetics,metabolism Humans Intercellular Signaling Peptides and Proteins/chemistry,genetics,metabolism Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Protein Binding
Chemicals
Intercellular Signaling Peptides and Proteins hepatoma-derived growth factor Histidine DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lukasik Stephen M
Department of Chemistry, University of Virginia, Charlottesville, VA 22906, USA.
Cierpicki Tomasz
Borloz Matthew
Grembecka Jolanta
Everett Allen
Bushweller John H
References (47)
47 references, click to expand
  1. Migration of smooth muscle and endothelial cells. Critical events in restenosis.
    Circulation. 1992 Sep;86(3):723-9 PMID: 1516183
  2. Cell signaling by receptor tyrosine kinases.
    Cell. 2000 Oct 13;103(2):211-25 PMID: 11057895
  3. Identification of novel, cardiac-restricted transcription factors binding to a CACC-box within the human cardiac troponin I promoter.
    Cardiovasc Res. 2001 Apr;50(1):24-33 PMID: 11282075
  4. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds.
    Nat Struct Biol. 2002 Mar;9(3):217-24 PMID: 11836534
  5. Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA.
    J Mol Biol. 2002 May 24;319(1):209-27 PMID: 12051947
  6. Antisense oligonucleotides of hepatoma-derived growth factor (HDGF) suppress the proliferation of hepatoma cells.
    Hepatogastroenterology. 2002 Nov-Dec;49(48):1639-44 PMID: 12397753
  7. Ciz1, Cip1 interacting zinc finger protein 1 binds the consensus DNA sequence ARYSR(0-2)YYAC.
    J Biomed Sci. 2003 Jul-Aug;10(4):406-17 PMID: 12824700
  8. Structural variation in PWWP domains.
    J Mol Biol. 2003 Jul 11;330(3):571-6 PMID: 12842472
  9. Mechanisms controlling EGF receptor endocytosis and degradation.
    Biochem Soc Trans. 2003 Dec;31(Pt 6):1178-81 PMID: 14641021
  10. Yin and Yang of an endothelial cell: from normal to the extreme in growth, secretion, and transdifferentiation capabilities.
    Paediatr Respir Rev. 2004;5 Suppl A:S253-7 PMID: 14980281
  11. Hepatoma-derived growth factor is a pulmonary endothelial cell-expressed angiogenic factor.
    Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1194-201 PMID: 14751852
  12. Chromatin targeting of de novo DNA methyltransferases by the PWWP domain.
    J Biol Chem. 2004 Jun 11;279(24):25447-54 PMID: 14998998
  13. Hepatoma-derived growth factor is a neurotrophic factor harbored in the nucleus.
    J Biol Chem. 2004 Jun 25;279(26):27320-6 PMID: 15140875
  14. Expression of hepatoma-derived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer.
    J Clin Oncol. 2004 Aug 15;22(16):3230-7 PMID: 15310766
  15. The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin.
    Mol Cell Biol. 2004 Oct;24(20):9048-58 PMID: 15456878
  16. Solution structure and heparin interaction of human hepatoma-derived growth factor.
    J Mol Biol. 2004 Nov 5;343(5):1365-77 PMID: 15491618
  17. Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3728-32 PMID: 3012531
  18. Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7311-5 PMID: 3020543
  19. Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing.
    Cell. 1987 Oct 23;51(2):199-209 PMID: 3499230
  20. Human vascular smooth muscle cells both express and respond to heparin-binding growth factor I (endothelial cell growth factor).
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7124-8 PMID: 2444975
  21. Translocation of bFGF to the nucleus is G1 phase cell cycle specific in bovine aortic endothelial cells.
    EMBO J. 1990 May;9(5):1511-7 PMID: 2328724
  22. Localization of peptide growth factors in the nucleus.
    Methods Enzymol. 1991;198:480-94 PMID: 1857237
  23. Density-dependent endothelial cell production of an inhibitor of smooth muscle cell growth.
    J Cell Biochem. 1993 Sep;53(1):21-31 PMID: 8227180
  24. Use of a selection technique to identify the diversity of binding sites for the yeast RAP1 transcription factor.
    Nucleic Acids Res. 1994 Jan 25;22(2):124-30 PMID: 8121795
  25. Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation.
    Mol Cell Biol. 1994 Jun;14(6):3938-48 PMID: 7910944
  26. Molecular cloning of complementary DNA for a novel human hepatoma-derived growth factor. Its homology with high mobility group-1 protein.
    J Biol Chem. 1994 Oct 7;269(40):25143-9 PMID: 7929202
  27. Measurement of HN-H alpha J couplings in calcium-free calmodulin using new 2D and 3D water-flip-back methods.
    J Biomol NMR. 1994 Nov;4(6):871-8 PMID: 7812158
  28. Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
    Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36 PMID: 7584402
  29. NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
    J Biomol NMR. 1995 Nov;6(3):277-93 PMID: 8520220
  30. How to measure and predict the molar absorption coefficient of a protein.
    Protein Sci. 1995 Nov;4(11):2411-23 PMID: 8563639
  31. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR.
    J Biomol NMR. 1996 Dec;8(4):477-86 PMID: 9008363
  32. An endothelial growth factor involved in rat renal development.
    J Clin Invest. 1998 Sep 15;102(6):1208-19 PMID: 9739055
  33. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  34. Overcoming expression and purification problems of RhoGDI using a family of "parallel" expression vectors.
    Protein Expr Purif. 1999 Feb;15(1):34-9 PMID: 10024467
  35. Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a multiprotein transcriptional complex required for activity of the human cardiac alpha-actin promoter.
    Mol Cell Biol. 1999 Apr;19(4):2577-84 PMID: 10082523
  36. GRASS: a server for the graphical representation and analysis of structures.
    Protein Sci. 1999 Mar;8(3):676-9 PMID: 10091670
  37. The CACC box and myocyte enhancer factor-2 sites within the myosin light chain 2 slow promoter cooperate in regulating nerve-specific transcription in skeletal muscle.
    J Biol Chem. 1999 Apr 23;274(17):12095-102 PMID: 10207035
  38. Protein backbone angle restraints from searching a database for chemical shift and sequence homology.
    J Biomol NMR. 1999 Mar;13(3):289-302 PMID: 10212987
  39. Binding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein.
    Mol Cell Biol. 2004 Dec;24(23):10470-8 PMID: 15542854
  40. Charged gels as orienting media for measurement of residual dipolar couplings in soluble and integral membrane proteins.
    J Am Chem Soc. 2004 Dec 15;126(49):16259-66 PMID: 15584763
  41. Solution structure of the PWWP domain of the hepatoma-derived growth factor family.
    Protein Sci. 2005 Mar;14(3):756-64 PMID: 15689505
  42. Hepatoma-derived growth factor as a prognostic marker in completely resected non-small-cell lung cancer.
    Oncol Rep. 2005 Jun;13(6):1075-80 PMID: 15870924
  43. Activation of p38 has opposing effects on the proliferation and migration of endothelial cells.
    J Biol Chem. 2005 Jun 3;280(22):20995-1003 PMID: 15790570
  44. VEGF189 stimulates endothelial cells proliferation and migration in vitro and up-regulates the expression of Flk-1/KDR mRNA.
    Exp Cell Res. 2005 Sep 10;309(1):24-31 PMID: 15996656
  45. Hepatoma-derived growth factor stimulates smooth muscle cell growth and is expressed in vascular development.
    J Clin Invest. 2000 Mar;105(5):567-75 PMID: 10712428
  46. The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation?
    FEBS Lett. 2000 May 4;473(1):1-5 PMID: 10802047
  47. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.
    J Clin Invest. 1993 Jan;91(1):94-8 PMID: 8380817
Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
0961-8368
DOI
10.1110/ps.051751706
Published
2006-02-00
Epub
2005-00-29
Pages
314-23
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2242466
Subset
IM
Databases
PDB
2B8A
External Links
PubMed source DOI: 10.1110/ps.051751706 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2