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

@article{Wiesmann1999CrystalSO,
  title={Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor},
  author={Christian Wiesmann and Mark Ultsch and Steven H. Bass and Abraham M. de Vos},
  journal={Nature},
  year={1999},
  volume={401},
  pages={184-188}
}
Nerve growth factor (NGF) is involved in a variety of processes involving signalling, such as cell differentiation and survival, growth cessation and apoptosis of neurons. These events are mediated by NGF as a result of binding to its two cell-surface receptors, TrkA and p75 (ref. 2). TrkA is a receptor with tyrosine kinase activity that forms a high-affinity binding site for NGF. Of the five domains comprising its extracellular portion, the immunoglobulin-like domain proximal to the membrane… 
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Identification and structure of the nerve growth factor binding site on TrkA.
TLDR
This work has expressed the second Ig-like domain as a recombinant protein in E. coli and demonstrated that NGF binds to this domain with similar affinity to the native receptor, TrkA, and presented the three-dimensional structure of the TrkAIg(2) domain in a new crystal form, refined to 2.0 A resolution.
Structural basis of the transmembrane domain dimerization and rotation in the activation mechanism of the TRKA receptor by nerve growth factor
TLDR
The TRKA–TMD can form dimers, the structural determinants of the dimer interface in the active receptor are identified, and this interface is validated through site-directed mutagenesis together with functional and cell differentiation studies.
Structural and Mechanistic Insights into Nerve Growth Factor Interactions with the TrkA and p75 Receptors
Structure of Nerve Growth Factor Complexed with the Shared Neurotrophin Receptor p75
TLDR
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.
Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5.
TrkA Amino Acids Controlling Specificity for Nerve Growth Factor*
TLDR
A minimum set of residues in the human TrkC second immunoglobulin-like domain, which does not bind nerve growth factor (NGF), were substituted with those from human TrKA and the resulting Trk variant recruited binding of NGF equivalent to TrkA, maintained neurotrophin-3 binding equivalent totrkC, and also bound brain-derived neurotrophins, although with lower affinity compared with TrkB.
TrkA Immunoglobulin-Like Ligand Binding Domains Inhibit Spontaneous Activation of the Receptor
TLDR
The data suggest that spontaneous Dimerization of TrkA occurs when the structure of the Ig-like domains is altered, implying that the intact domains inhibit receptor dimerization in the absence of NGF.
Structural Basis and Mechanism of TrkA Activation by NGF through Ligand-Induced Rotation of Transmembrane Domain Dimers
TLDR
The data indicate that the transmembrane and juxtamembrane regions of the receptor play a key role in the dimerization and conformational activation of TrkA by NGF.
Structural Basis of the Transmembrane Domain Dimerization in the Activation Mechanism of TrkA by NGF
TLDR
The data indicates that the transmembrane and juxtamembrane regions of the receptor play a key role in the dimerization and activation of TrkA by NGF.
The Mechanism of NGF Signaling Suggested by the p75 and TrkA Receptor Complexes
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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