Premium
Oligomerization of acidic fibroblast growth factor is not a prerequisite for its cell proliferation activity
Author(s) -
Arunkumar Alphonse I.,
Kumar Thallampuranam Krishnaswamy S.,
Kathir Karuppanan Muthusamy,
Srisailam Sampath,
Wang HanMin,
Leena Philominathan Sagaya Theresa,
Chi YaHui,
Chen HoChz,
Wu ChiehHsi,
Wu RongTsun,
Chang GuGang,
Chiu IngMing,
Yu Chin
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.2270102
Subject(s) - chemistry , biophysics , fibroblast growth factor , cell growth , plasma protein binding , ligand (biochemistry) , biochemistry , receptor , iduronic acid , monomer , heparan sulfate , nuclear overhauser effect , protein–protein interaction , nuclear magnetic resonance spectroscopy , heparin , stereochemistry , biology , organic chemistry , polymer
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. 15 N and 1 H 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.