Nerve growth factor: Structure/function relationships

Authors

  • Ralph A. Bradshaw,

    Corresponding author
    1. Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92717
    • Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92717
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  • Judith Murray-Rust,

    1. ICRF Unit for Structural Molecular Biology, Department of Crystallography, Birkbeck College, Malet Street, London WCIE 7HX, United Kingdom
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  • Tom L. Blundell,

    1. ICRF Unit for Structural Molecular Biology, Department of Crystallography, Birkbeck College, Malet Street, London WCIE 7HX, United Kingdom
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  • Neil Q. Mcdonald,

    1. ICRF Unit for Structural Molecular Biology, Department of Crystallography, Birkbeck College, Malet Street, London WCIE 7HX, United Kingdom
    Current affiliation:
    1. Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032
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  • Risto Lapatto,

    1. ICRF Unit for Structural Molecular Biology, Department of Crystallography, Birkbeck College, Malet Street, London WCIE 7HX, United Kingdom
    Current affiliation:
    1. Department of Medical Chemistry, Siltavuorenpenger 10, Helsinki, Finland
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  • Carlos F. Ibáñez

    1. Department of Medical Chemistry, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden
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Abstract

Nerve growth factor (NGF), which has a tertiary structure based on a cluster of 3 cystine disulfides and 2 very extended, but distorted β-hairpins, is the prototype of a larger family of neurotrophins. Prior to the availability of cloning techniques, the mouse submandibular gland was the richest source of NGF and provided sufficient material to enable its biochemical characterization. It binds as a dimer to at least 2 cell-surface receptor types expressed in a variety of neuronal and non-neuronal cells. Residues involved in these interactions and in the maintenance of tertiary and quaternary structure have been identified by chemical modification and site-directed mutagenesis, and this information can be related to their location in the 3-dimensional structure. For example, interactions between aromatic residues contribute to the stability of the NGF dimer, and specific surface lysine residues participate in receptor contacts. The conclusion from these studies is that receptor interactions involve broad surface regions, which may be composed of residues from both protomers in the dimer.

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