A study of fibroblast growth factor and its receptor complex using light scattering
by Sharma, Pallavi; Rajalingam, Dakshinamurthy; Kumar, T. K. S.; Singh, Surendra
Fibroblast growth factors (FGFs) are a family of proteins that participate in key cellular process such as cell proliferation and differentiation. They exert their biological activity by binding to their cell surface tyrosine kinase receptors (FGFRs), which contain an extracellular domain consisting of three structural sub-domains called D1, D2, and D3. Mutational studies have shown that the D2 sub-domain contributes to the ligand (FGF) binding. Studies of FGF-FGFR complex using crystallographic techniques and sizeexclusion chromatography (SEC) suggest different stoichiometry for the FGF-FGFR complex. We have used dynamical light scattering to study the interaction between fibroblast growth factor (FGF) and its receptor [1]. A simple model based on reaction dynamics was used to determine the concentration of product formed by the interaction of two proteins and its dependence on the initial concentration of interacting proteins. Calculated hydrodynamic diameters reveal that both human fibroblast growth factor (hFGF-1), and its receptor domain (D2 domain) exist as monomers in solution. Titration of hFGF-1 and the D2 domain of FGFR, show that they interact in a 1:1 stoichiometry in solution. The binding stoichiometry does depend the concentrations of the interacting proteins. These studies suggest that the dimer interface observed in the crystal structures of the FGF-FGFR complex is a crystallization artifact. A 2:2 binary complex of FGF and FGFR seen in the crystal structures is not observed in solution.
- Conference
- Frontiers in Optics, FiO 2009
- Year
- 2009
- URL
- https://dx.doi.org/10.1364/fio.2009.jwc66
- ISBN/ISSN
- 2162-2701
- DOI
- 10.1364/fio.2009.jwc66