Bradshaw R A, Murray-Rust J, Ibáñez C F, McDonald N Q, Lapatto R, Blundell T L
Department of Biological Chemistry, College of Medicine, University of California, Irvine 92717.
Protein Sci. 1994 Nov;3(11):1901-13. doi: 10.1002/pro.5560031102.
Nerve growth factor (NGF), which has a tertiary structure based on a cluster of 3 cystine disulfides and 2 very extended, but distorted beta-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 promoters in the dimer.
神经生长因子（NGF）是更大的神经营养因子家族的原型，其三级结构基于一组3个胱氨酸二硫键和2个非常伸展但扭曲的β-发夹结构。在克隆技术出现之前，小鼠下颌下腺是NGF最丰富的来源，并提供了足够的材料以对其进行生化特性鉴定。它以二聚体形式与多种神经元和非神经元细胞中表达的至少2种细胞表面受体类型结合。通过化学修饰和定点诱变已鉴定出参与这些相互作用以及维持三级和四级结构的残基，并且该信息可与其在三维结构中的位置相关。例如，芳香族残基之间的相互作用有助于NGF二聚体的稳定性，特定的表面赖氨酸残基参与受体接触。这些研究得出的结论是，受体相互作用涉及广泛的表面区域，这些区域可能由二聚体中两个启动子的残基组成。
