Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity

Alphonse I. Arunkumar, Thallampuranam Krishnaswamy S Kumar, Karuppanan Muthusamy Kathir, Sampath Srisailam, Han Min Wang, Philominathan Sagaya Theresa Leena, Ya Hui Chi, Ho Chz Chen, Chieh Hsi Wu, Rong Tsun Wu, Gu Gang Chang, Ing Ming Chiu, Chin Yu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Oligomerization of fibroblast growth factors (FGFs) induced on binding to heparin or heparan sulfate proteoglycan is considered to be crucial for receptor activation and initiation of biological responses. To gain insight into the mechanism of activation of the receptor by FGFs, in the present study we investigate the effect(s) of interaction of a heparin analog, sucrose octasulfate (SOS), on the structure, stability, and biological activities of a recombinant acidic FGF from Notophthalmus viridescens (nFGF-1). SOS is found to bind to nFGF-1 and significantly increase the thermodynamic stability of the protein. Using a variety of techniques such as size-exclusion chromatography, sedimentation velocity, and multidimensional nuclear magnetic resonance (NMR) spectroscopy, it is shown that binding of SOS to nFGF-1 retains the protein in its monomeric state. In its monomeric state (complexed to SOS), n-FGF-1 shows significant cell proliferation activity. 15N and 1H chemical shift perturbation and the intermolecular nuclear Overhauser effects (NOEs) between SOS and nFGF-1 reveal that the ligand binds to the dense, positively charged cluster located in the groove enclosed by β-strands 10 and 11. In addition, molecular modeling based on the NOEs observed for the SOS-nFGF-1 complex, indicates that SOS and heparin share a common binding site on the protein. In conclusion, the results of the present study clearly show that heparin-induced oligomerization of nFGF-1 is not mandatory for its cell proliferation activity.

Original languageEnglish
Pages (from-to)1050-1061
Number of pages12
JournalProtein Science
Volume11
Issue number5
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 1
Oligomerization
Cell proliferation
Cell Proliferation
Heparin
Notophthalmus viridescens
Chemical activation
Fibroblast Growth Factor Receptors
Heparan Sulfate Proteoglycans
Proteins
Molecular modeling
Fibroblast Growth Factors
Size exclusion chromatography
Protein Stability
Chemical shift
Bioactivity
sucrose octasulfate
Thermodynamics
Sedimentation
Nuclear magnetic resonance spectroscopy

Keywords

  • β-barrel
  • Heparin binding
  • nFGF-1
  • Oligomerization
  • Receptor
  • Stability

ASJC Scopus subject areas

  • Biochemistry

Cite this

Arunkumar, A. I., Kumar, T. K. S., Kathir, K. M., Srisailam, S., Wang, H. M., Leena, P. S. T., ... Yu, C. (2002). Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity. Protein Science, 11(5), 1050-1061. https://doi.org/10.1110/ps.2270102

Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity. / Arunkumar, Alphonse I.; Kumar, Thallampuranam Krishnaswamy S; Kathir, Karuppanan Muthusamy; Srisailam, Sampath; Wang, Han Min; Leena, Philominathan Sagaya Theresa; Chi, Ya Hui; Chen, Ho Chz; Wu, Chieh Hsi; Wu, Rong Tsun; Chang, Gu Gang; Chiu, Ing Ming; Yu, Chin.

In: Protein Science, Vol. 11, No. 5, 2002, p. 1050-1061.

Research output: Contribution to journalArticle

Arunkumar, AI, Kumar, TKS, Kathir, KM, Srisailam, S, Wang, HM, Leena, PST, Chi, YH, Chen, HC, Wu, CH, Wu, RT, Chang, GG, Chiu, IM & Yu, C 2002, 'Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity', Protein Science, vol. 11, no. 5, pp. 1050-1061. https://doi.org/10.1110/ps.2270102
Arunkumar, Alphonse I. ; Kumar, Thallampuranam Krishnaswamy S ; Kathir, Karuppanan Muthusamy ; Srisailam, Sampath ; Wang, Han Min ; Leena, Philominathan Sagaya Theresa ; Chi, Ya Hui ; Chen, Ho Chz ; Wu, Chieh Hsi ; Wu, Rong Tsun ; Chang, Gu Gang ; Chiu, Ing Ming ; Yu, Chin. / Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity. In: Protein Science. 2002 ; Vol. 11, No. 5. pp. 1050-1061.
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AU - Srisailam, Sampath

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AU - Leena, Philominathan Sagaya Theresa

AU - Chi, Ya Hui

AU - Chen, Ho Chz

AU - Wu, Chieh Hsi

AU - Wu, Rong Tsun

AU - Chang, Gu Gang

AU - Chiu, Ing Ming

AU - Yu, Chin

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