Neurotrophic factor structures reveal clues to evolution, binding, specificity, and receptor activation.
The neutrophin family, the glial-derived neurotrophic factor family, and the ciliary neurotrophic factor are the best described growth factors specific for developing neurons and neutral crest cells. As might be expected for regulatory molecules of the complex central and peripheral nervous system, these factors show considerable receptor specificity and cross-talk. Thanks to a decade of intense research by numerous laboratories, the structures of many of these factors are now available. This review discusses the structural bases of receptor binding, specificity, and activation in each of these systems. Using structure-based sequence alignments, the evolutionary implications of these molecules and their receptors are discussed, followed by suggestions for further directions for research on the structure and function of these neurotrophic factors.
Butte
M J
MJ
University of California San Francisco, Department of Biochemistry and Biophysics, 94143-0448, USA. manish@msg.ucsf.edu
D000595:Amino Acid Sequence; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000737:chemistry; D019143:Evolution, Molecular; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D016415:Sequence Alignment
D020934:Ciliary Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor