PWWP Module of Human Hepatoma-derived Growth Factor Forms a Domain-swapped Dimer with Much Higher Affinity for Heparin

Shih Che Sue, Wei Tin Lee, Shi Chi Tien, Shao Chen Lee, Jiun Guo Yu, Wen Jin Wu, Wen guey Wu, Tai huang Huang

Research output: Contribution to journalArticle

24 Citations (Scopus)


Hepatoma-derived growth factor (hHDGF)-related proteins (HRPs) comprise a new growth factor family sharing a highly conserved and ordered N-terminal PWWP module (residues 1-100, previously referred to as a HATH domain) and a variable disordered C-terminal domain. We have shown that the PWWP module is responsible for heparin binding and have solved its structure in solution. Here, we show that under physiological conditions, both the PWWP module and hHDGF can form dimers. Surface plasmon resonance (SPR) studies revealed that the PWWP dimer binds to heparin with affinity that is two orders of magnitude higher (Kd = 13 nM) than that of the monomeric PWWP module (Kd = 1.2 μM). The monomer-dimer equilibrium properties and NMR structural data together suggest that the PWWP dimer is formed through a domain-swapping mechanism. The domain-swapped PWWP dimer structures were calculated on the basis of the NMR data. The results show that the two PWWP protomers exchange their N-terminal hairpin to form a domain-swapped dimer. The two monomers in a dimer are linked by the long flexible L2 loops, a feature supported by NMR relaxation data for the monomer and dimer. The enhanced heparin-binding affinity of the dimer can be rationalized in the framework of the dimer structure.

Original languageEnglish
Pages (from-to)456-472
Number of pages17
JournalJournal of Molecular Biology
Issue number2
Publication statusPublished - 2007 Mar 23



  • HATH domain
  • HDGF
  • domain swapping
  • growth factor
  • heparin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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