Dimeric Structure and Conformational Stability of Brain-Derived Neurotrophic Factor and Neurotrophin-3

Czeslaw Radziejewski; Robert C. Robinson; Peter S. DiStefano; John W. Taylor

doi:10.1021/bi00133a007

Dimeric Structure and Conformational Stability of Brain-Derived Neurotrophic Factor and Neurotrophin-3

Czeslaw Radziejewski, Robert C. Robinson, Peter S. DiStefano, John W. Taylor

Research output: Contribution to journal › Article › peer-review

65 Citations (Scopus)

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 farultraviolet 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 ofdenaturant. Circular dichroism spectroscopy revealed approximately 70% β-sheet and 20% β-turn content in the native structure ofboth neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.

Original language	English
Pages (from-to)	4431-4436
Number of pages	6
Journal	Biochemistry
Volume	31
Issue number	18
DOIs	https://doi.org/10.1021/bi00133a007
Publication status	Published - Jan 1 1992
Externally published	Yes

ASJC Scopus subject areas

Biochemistry

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10.1021/bi00133a007

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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 farultraviolet 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 ofdenaturant. Circular dichroism spectroscopy revealed approximately 70% β-sheet and 20% β-turn content in the native structure ofboth neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.",

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AU - Radziejewski, Czeslaw

AU - Robinson, Robert C.

AU - DiStefano, Peter S.

AU - Taylor, John W.

PY - 1992/1/1

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N2 - 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 farultraviolet 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 ofdenaturant. Circular dichroism spectroscopy revealed approximately 70% β-sheet and 20% β-turn content in the native structure ofboth neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.

AB - 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 farultraviolet 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 ofdenaturant. Circular dichroism spectroscopy revealed approximately 70% β-sheet and 20% β-turn content in the native structure ofboth neurotrophic factors. In this respect, BDNF and NT-3 resemble other polypeptide growth factors whose receptors are also integral protein-tyrosine kinases.

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Dimeric Structure and Conformational Stability of Brain-Derived Neurotrophic Factor and Neurotrophin-3

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