Database accession: MF2100008
Name: Neurotrophin 4 homodimer
PDB ID: 1b98
Experimental method: X-ray (2.75 Å)
Assembly: homodimer
Source organism: Homo sapiens
Primer publication of the structure:
Robinson RC, Radziejewski C, Spraggon G, Greenwald J, Kostura MR, Burtnick LD, Stuart DI, Choe S, Jones EY
The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site.
(1999) Protein Sci. 8: 2589-97
PMID: 10631974
Abstract:
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.
Molecular function:
neurotrophin p75 receptor binding Interacting selectively and non-covalently with the neurotrophin p75 receptor.
growth factor activity The function that stimulates a cell to grow or proliferate. Most growth factors have other actions besides the induction of cell growth or proliferation.
Biological process:
taste bud development The progression of the taste bud over time, from its formation to the mature state. The taste bud is a specialized area of the tongue that contains taste receptors.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
mechanoreceptor differentiation The process in which a relatively unspecialized cell acquires specialized features of a mechanoreceptor, a cell specialized to transduce mechanical stimuli and relay that information centrally in the nervous system.
ganglion mother cell fate determination The cell fate determination process in which a cell becomes capable of differentiating autonomously into a ganglion mother cell regardless of its environment; upon determination, the cell fate cannot be reversed.
neuron projection morphogenesis The process in which the anatomical structures of a neuron projection are generated and organized. A neuron projection is any process extending from a neural cell, such as axons or dendrites.
innervation The process in which a nerve invades a tissue and makes functional synaptic connection within the tissue.
sensory organ boundary specification The process in which boundaries between a sensory organ and the surrounding tissue are established and maintained.
adult locomotory behavior Locomotory behavior in a fully developed and mature organism.
regulation of neuron differentiation Any process that modulates the frequency, rate or extent of neuron differentiation.
transmembrane receptor protein tyrosine kinase signaling pathway A series of molecular signals initiated by the binding of an extracellular ligand to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with regulation of a downstream cellular process, e.g. transcription.
Cellular component:
cytoplasmic, membrane-bounded vesicle A membrane-bounded vesicle found in the cytoplasm of the cell.
endoplasmic reticulum lumen The volume enclosed by the membranes of the endoplasmic reticulum.
Entry contents: 2 distinct polypeptide molecules
Chains: A, M
Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.
Number of unique protein segments: 1
Name: Neurotrophin-4
Source organism: Homo sapiens
Length: 130 residues
Sequence:Sequence according to PDB SEQRESGVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
UniProtKB AC: P34130 (positions: 81-210)
Coverage: 61.9%UniRef90 AC: UniRef90_P34130 (positions: 81-210)
Name: Neurotrophin-4
Source organism: Homo sapiens
Length: 130 residues
Sequence:Sequence according to PDB SEQRESGVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEVLGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRALTADAQGRVGWRWIRIDTACVCTLLSRTGRA
UniProtKB AC: P34130 (positions: 81-210)
Coverage: 61.9%UniRef90 AC: UniRef90_P34130 (positions: 81-210)
Complex evidence:
Various dimeric members of neurotrophic factors (including human/mouse nerve growth factor, human brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)) have been shown to fold and dimerize at the same time via a two-state process (PMID: 8161524). While the members of this family show a significant variance in sequence, they adopt a highly similar structure upon binding and behave almost identically in unfolding/refolding experiments. Thus the two-state folding/binding nature seems to be a hallmark of NGF and closely related proteins.