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

• Published in: Protein science Vol. 8; no. 12; pp. 2589 - 2597
• Main Authors: ROBINSON, ROBERT C., RADZIEJEWSKI, CZESLAW, SPRAGGON, GLEN, GREENWALD, JASON, KOSTURA, MIKEY R., BURTNICK, LESLIE D., STUART, DAVID I., CHOE, SENYON, JONES, E. YVONNE
• Format: Journal Article
• Language: English
• Published: Bristol Cambridge University Press 01-12-1999; Cold Spring Harbor Laboratory Press
• Subjects: Binding Sites; Brain-Derived Neurotrophic Factor - chemistry; Crystallization; crystallography; Crystallography, X-Ray; Humans; Molecular Sequence Data; nerve growth factor; Nerve Growth Factors - chemistry; Protein Structure, Quaternary; receptor; Receptor Protein-Tyrosine Kinases - chemistry; Receptor, Nerve Growth Factor - chemistry; nerve growth factor; crystallography; receptor
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.8.12.2589

The neurotrophins are growth factors that are involved
in the development and 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 mediated through trk cell surface receptors. We have
determined the structures of the heterodimer formed between
brain-derived neurotrophic factor (BDNF) and neurotrophin
4 (NT4), as well as the structure of homodimer of NT4.
We also present the structure of the Neurotrophin 3 homodimer,
which is refined to higher resolution than previously published.
These structures provide the first views of the architecture
of the NT4 protomer. Comparison of the surface of a model
of the BDNF homodimer with the structures of the neurotrophin
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
periphery of this common region serve to confer trk receptor
specificity.