The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site

Citation
Rc. Robinson et al., The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site, PROTEIN SCI, 8(12), 1999, pp. 2589-2597
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
8
Issue
12
Year of publication
1999
Pages
2589 - 2597
Database
ISI
SICI code
0961-8368(199912)8:12<2589:TSOTN4>2.0.ZU;2-Q
Abstract
The neurotrophins are growth factors that are involved in the development a nd survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediat ed through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) an d neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We al so present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide th e first views of the architecture of the NT4 protomer. Comparison of the su rface of a model of the BDNF homodimer with the structures of the neurotrop hin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the peripher y of this common region serve to confer trk receptor specificity.