General Information

Database accession: MF2100008

Name: Neurotrophin 4 homodimer

PDB ID: 1b98 PDB

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 PubMed


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.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

neurotrophin p75 receptor binding Interacting selectively and non-covalently with the neurotrophin p75 receptor. GeneOntology

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. GeneOntology

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. GeneOntology

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. GeneOntology

epidermis development The process whose specific outcome is the progression of the epidermis over time, from its formation to the mature structure. The epidermis is the outer epithelial layer of an animal, it may be a single layer that produces an extracellular material (e.g. the cuticle of arthropods) or a complex stratified squamous epithelium, as in the case of many vertebrate species. GeneOntology

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. GeneOntology

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. GeneOntology

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. GeneOntology

long-term memory The memory process that deals with the storage, retrieval and modification of information a long time (typically weeks, months or years) after receiving that information. This type of memory is typically dependent on gene transcription regulated by second messenger activation. GeneOntology

innervation The process in which a nerve invades a tissue and makes functional synaptic connection within the tissue. GeneOntology

sensory organ boundary specification The process in which boundaries between a sensory organ and the surrounding tissue are established and maintained. GeneOntology

adult locomotory behavior Locomotory behavior in a fully developed and mature organism. GeneOntology

cell-cell signaling Any process that mediates the transfer of information from one cell to another. This process includes signal transduction in the receiving cell and, where applicable, release of a ligand and any processes that actively facilitate its transport and presentation to the receiving cell. Examples include signaling via soluble ligands, via cell adhesion molecules and via gap junctions. GeneOntology

regulation of neuron differentiation Any process that modulates the frequency, rate or extent of neuron differentiation. GeneOntology

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. GeneOntology

Cellular component:

cytoplasmic, membrane-bounded vesicle A membrane-bounded vesicle found in the cytoplasm of the cell. GeneOntology

extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. GeneOntology

endoplasmic reticulum lumen The volume enclosed by the membranes of the endoplasmic reticulum. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

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

Chain A

Name: Neurotrophin-4

Source organism: Homo sapiens

Length: 130 residues


UniProtKB AC: P34130 (positions: 81-210) UniProt Coverage: 61.9%

UniRef90 AC: UniRef90_P34130 (positions: 81-210) UniRef90

Chain M

Name: Neurotrophin-4

Source organism: Homo sapiens

Length: 130 residues


UniProtKB AC: P34130 (positions: 81-210) UniProt Coverage: 61.9%

UniRef90 AC: UniRef90_P34130 (positions: 81-210) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

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.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

There is 1 related structure in the Protein Data Bank:

The molecule viewer shows the original PDB stucture.

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