Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex

  title={Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex},
  author={Yong Gong and Peng Cao and Hong Yu and Tao Jiang},
Neurotrophins (NTs) are important regulators for the survival, differentiation and maintenance of different peripheral and central neurons. NTs bind to two distinct classes of glycosylated receptor: the p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptors (Trks). Whereas p75NTR binds to all NTs, the Trk subtypes are specific for each NT. The question of whether NTs stimulate p75NTR by inducing receptor homodimerization is still under debate. Here we report the 2.6-Å resolution… 

Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation

Investigation of the oligomerization state of p75NTR begins to provide insights to the mechanisms of signal initiation of this noncatalytic receptor, as well as to develop therapeutic interventions to diminish its activity.

The TrK Receptor Family

The Trk receptors primarily bind and signal through Shc, FRS2, and PLCγ, which in turn activate PI3K, the Erks, and the hydrolysis of inositol phospholipids, leading to the modulation of gene transcription.

An Intracellular Domain Fragment of the p75 Neurotrophin Receptor (p75NTR) Enhances Tropomyosin Receptor Kinase A (TrkA) Receptor Function*

A specific 29-amino acid peptide derived from the intracellular domain fragment of p75NTR interacts with and potentiates binding of NGF to TrkA-expressing cells, leading to increased neurite outgrowth in sympathetic neurons as a result of enhanced Erk1/2 and Akt signaling.

Comparison of nerve growth factor receptor binding models using heterodimeric muteins

The data support the ligand passing of NGF from p75 to TrkA involving a transient heteroreceptor complex of p75‐NGF‐TrkA.

The conundrum of the high-affinity NGF binding site formation unveiled?

High-affinity TrkA and p75 neurotrophin receptor complexes: A twisted affair




Crystal structure of neurotrophin-3 homodimer shows distinct regions are used to bind its receptors.

A comparison of the dimer interface between the NT-3 homodimer and the BDNF/NT-3 heterodimer reveals similar patterns of hydrogen bonds and nonpolar contacts, which reinforces the notion that the evolutionarily conserved neurotrophin interface resulted from the need for receptor dimerization in signal initiation.

Characterization of Symmetric Complexes of Nerve Growth Factor and the Ectodomain of the Pan-neurotrophin Receptor, p75NTR*

Following assembly and purification of soluble p75NTR·NGF complexes, mass spectrometry, analytical ultracentrifugation, and solution x-ray scattering measurements are indicative of 2:2 stoichiometry, which implies a symmetric complex.

Structure of Nerve Growth Factor Complexed with the Shared Neurotrophin Receptor p75

Neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex.

Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor

The structure of human NGF in complex with human TrkA-d5 is consistent with results from mutagenesis experiments for all neurotrophins, and indicates that the first patch may constitute a conserved binding motif for all family members, whereas the second patch is specific for the interaction between NGF and TrKA.

Neurotrophin-regulated signalling pathways

  • L. Reichardt
  • Biology
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2006
Three rare human genetic disorders, which result in deleterious effects on sensory perception, cognition and a variety of behaviours, have been shown to be attributable to mutations in brain-derived neurotrophic factor and two of the Trk receptors.

The dual nature of neurotrophins.

Recent studies have revealed an intriguing pattern: neurotrophins can elicit opposing signals utilising their variable configuration and different receptor types.

Growth factor receptors: structure, mechanism, and drug discovery.

Progress in the development of agonists or antagonists of the ligand for these receptors is discussed, with particular attention given to the transforming growth factor-alpha, epidermal growth factor; nerve growth factor, neurotrophin; and insulin-like growthfactor-1, insulin systems.

Binding of neurotrophin‐3 to its neuronal receptors and interactions with nerve growth factor and brain‐derived neurotrophic factor.

Specific high‐affinity NT‐3 receptors exist on sensory neurons that can readily discriminate between three structurally related ligands, including the remarkable property of the LANR to bind three related ligand with similar affinity, but different rate constants.

p75NTR – live or let die