Nerve Growth Factor W/ Binding Affinity & Signal Transduction Property

Saragovi, H U.

Abstract

Nerve growth factor (NGF) is a polypeptide growth factor that is a member of the neutrophin family which includes brain-derived neurotrophic factor, neutrophin 3, and neutrophin 4/5. Two cell surface NGF receptors have been characterized on the basis of binding affinity and signal transduction properties, namely the p75 low affinity NGF receptor and p140 TrkA. NGF dimerizes in solution and interacts with two or three TrkA receptors to form a high affinity complex with a dissociation constant of 10-9 M. Isothermal titration calorimetric studies are currently in progress to determine an exact stoichiometry for the NGF-TrkA complex and resultant enthalpy and free energy of binding. Preliminary results indicate that one NGF dimer binds two TrkA receptors with an enthalpy of - 4.8 kcal/mol TrkA.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Center for Research Resources (NCRR)
• Type: Biotechnology Resource Grants (P41)
• Project #: 5P41RR004328-10
• Application #: 6122048
• Project Start: 1997-08-05
• Project End: 1998-08-04
• Support Year: 10
• Fiscal Year: 1997

Institution

• Name: Johns Hopkins University
• DUNS #: 045911138
• City: Baltimore
• State: MD
• Country: United States
• Zip Code: 21218

Publications

Jaganaman, Sunil; Pinto, Alex; Tarasev, Michael et al. (2007) High levels of expression of the iron-sulfur proteins phthalate dioxygenase and phthalate dioxygenase reductase in Escherichia coli. Protein Expr Purif 52:273-9

Todd, M J; Gomez, J (2001) Enzyme kinetics determined using calorimetry: a general assay for enzyme activity? Anal Biochem 296:179-87

Karantza, V; Freire, E; Moudrianakis, E N (2001) Thermodynamic studies of the core histones: stability of the octamer subunits is not altered by removal of their terminal domains. Biochemistry 40:13114-23

Griko, Y V; Remeta, D P (1999) Energetics of solvent and ligand-induced conformational changes in alpha-lactalbumin. Protein Sci 8:554-61

Chu, V; Freitag, S; Le Trong, I et al. (1998) Thermodynamic and structural consequences of flexible loop deletion by circular permutation in the streptavidin-biotin system. Protein Sci 7:848-59

Luque, I; Freire, E (1998) Structure-based prediction of binding affinities and molecular design of peptide ligands. Methods Enzymol 295:100-27

Luque, I; Gomez, J; Semo, N et al. (1998) Structure-based thermodynamic design of peptide ligands: application to peptide inhibitors of the aspartic protease endothiapepsin. Proteins 30:74-85

Gomez, J; Semo, N; Freire, E (1998) Structural thermodynamic study of the binding of renin inhibitors to endothiapepsin. Adv Exp Med Biol 436:325-8

Koder, R L; Miller, A F (1998) Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif 13:53-60

Freire, E (1998) Statistical thermodynamic linkage between conformational and binding equilibria. Adv Protein Chem 51:255-79