title: Dimeric structure and conformational stability of brain-derived neurotrophic factor and neurotrophin-3.
abstract: We have examined the molecular structure of the related neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) by physical methods, including gel filtration, velocity sedimentation, sedimentation equilibrium, urea gel electrophoresis, fluorescence spectroscopy, and far-ultraviolet circular dichroism. The results of these studies indicate that at physiologically relevant concentrations both recombinant proteins exist as tightly associated dimers. The dimers are stable even in 8 M solutions of urea. In solutions of guanidine hydrochloride, BDNF and NT-3 undergo slow unfolding between 3 and 5 M concentration of denaturant. Circular dichroism spectroscopy revealed approximately 70% beta-sheet and 20% beta-turn content in the native structure of both neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.
authors.affiliation: Regeneron Pharmaceuticals Inc., Tarrytown, New York 10591.
authors.forename: C
authors.initials: C
authors.lastname: Radziejewski
authors.forename: R C
authors.initials: RC
authors.lastname: Robinson
authors.forename: P S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: J W
authors.initials: JW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor; D016466:CHO Cells; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006224:Cricetinae; D004586:Electrophoresis; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D020933:Neurotrophin 3; D011487:Protein Conformation; D011489:Protein Denaturation; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3