Solution structure and heparin interaction of human hepatoma-derived growth factor

Shih Che Sue, Jeou Yuan Chen, Shao Chen Lee, Wen Guey Wu, Tai-huang Huang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a new protein family that has been implicated in nephrogenesis, tumorigenesis, vascular development, cell proliferation, and transcriptional activation. All HRPs share a conserved N-terminal homologous to the amino terminus of HDGF (HATH) domain, but vary significantly in the C-terminal region. Here, we show that in solution the N and C termini of human HDGF form two structurally independent domains. The 100 amino acid residue N-terminal HATH domain is well-structured while the 140 amino acid residue C-terminal domain is disordered. We determined the solution structure of the HATH domain by NMR. The core structure of the HATH domain is a five-stranded β-barrel followed by two α-helices, similar to those of PWWP domains of known structures. Surface plasmon resonance results showed that the HATH domain is primarily responsible for heparin binding. On the basis of the chemical shift perturbation induced by binding of heparin-derived hexasaccharide, we identified a prominent, highly positively charged region as the putative heparin-binding site. Sequence comparison and structure prediction suggest that all HRPs are likely to adapt a similar modular structure.

Original languageEnglish
Pages (from-to)1365-1377
Number of pages13
JournalJournal of Molecular Biology
Volume343
Issue number5
DOIs
Publication statusPublished - 2004 Nov 5

Fingerprint

Heparin
Proteins
Amino Acids
Surface Plasmon Resonance
Transcriptional Activation
Blood Vessels
Carcinogenesis
Binding Sites
Cell Proliferation
hepatoma-derived growth factor

Keywords

  • HDGF
  • NMR structure
  • PWWP domain
  • growth factor
  • heparin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Solution structure and heparin interaction of human hepatoma-derived growth factor. / Sue, Shih Che; Chen, Jeou Yuan; Lee, Shao Chen; Wu, Wen Guey; Huang, Tai-huang.

In: Journal of Molecular Biology, Vol. 343, No. 5, 05.11.2004, p. 1365-1377.

Research output: Contribution to journalArticle

Sue, Shih Che ; Chen, Jeou Yuan ; Lee, Shao Chen ; Wu, Wen Guey ; Huang, Tai-huang. / Solution structure and heparin interaction of human hepatoma-derived growth factor. In: Journal of Molecular Biology. 2004 ; Vol. 343, No. 5. pp. 1365-1377.
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