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Nerve growth factor: Structure/function relationships
Author(s) -
Bradshaw Ralph A.,
MurrayRust Judith,
Blundell Tom L.,
Mcdonald Neil Q.,
Lapatto Risto,
Ibáñez Carlos F.
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560031102
Subject(s) - dimer , nerve growth factor , receptor , chemistry , protein tertiary structure , mutagenesis , neurotrophin , biochemistry , biophysics , stereochemistry , microbiology and biotechnology , biology , mutation , organic chemistry , gene
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.