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

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 藥學院 > 藥學系暨碩博士班 > 期刊論文 > Item 310903500/7687

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题名:	Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity
作者:	( Arunkumar A.);(Kumar T.K.S.);(Kathir K.M.);(Srisailam S.);(Wang H.M.);(Leena P.S.T.);(Chi Y.H.);(Chen H.C.);吳介信(Chieh-Hsi Wu);(Wu R.T.)
贡献者:	藥學院藥學系;中國附醫醫學研究部
日期:	2002-05
上传时间:	2009-08-26 16:33:48 (UTC+8)
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.
關聯:	PROTEIN SCIENCE 11(5 )1050 ~1061
显示于类别:	[藥學系暨碩博士班] 期刊論文

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