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

研究成果: 雜誌貢獻文章同行評審

28 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1050-1061
頁數12
期刊Protein Science
11
發行號5
DOIs
出版狀態已發佈 - 2002
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry

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