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| '''High affinity nerve growth factor receptor''' (TrkA) is a tyrosine kinase receptor. TrkA ligand - nerve growth factor activates the receptor by stabilizing homodimer formation which initiates transautophosphorylation<ref name="TrkA">PMID:9759973</ref>. | | '''High affinity nerve growth factor receptor''' (TrkA) is a tyrosine kinase receptor. Trk stands for Topomyosin-Related Kinase. TrkA ligand - nerve growth factor activates the receptor by stabilizing homodimer formation which initiates transautophosphorylation<ref name="TrkA">PMID:9759973</ref>. |
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| == Relevance == | | == Relevance == |
Revision as of 08:50, 1 January 2019
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Function
High affinity nerve growth factor receptor (TrkA) is a tyrosine kinase receptor. Trk stands for Topomyosin-Related Kinase. TrkA ligand - nerve growth factor activates the receptor by stabilizing homodimer formation which initiates transautophosphorylation[1].
Relevance
TrkA has a role in the pathogenesis of psoriasis and its inhibitors are studied in the development of novel therapeutics for the disease[1]. TrkA inhibition may be a novel therapeutic approach to Alzheimer disease[2] and a new method to treat intractable pain[3].
Structural highlights
Structure of Nerve Growth Factor Complexed with the Extracellular Domain of TrkA. An Arg residue, conserved in all neutrophins, forms the most important binding determinant between TrkA and its ligand - nerve growth factor - which forms the active homodimer of the receptor[4], [5]. All interactions between TrkA chain A and NGF.
- ↑ 1.0 1.1 Gill JS, Windebank AJ. Direct activation of the high-affinity nerve growth factor receptor by a non-peptide symmetrical polyanion. Neuroscience. 1998 Dec;87(4):855-60. PMID:9759973
- ↑ Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. doi: 10.3233/JAD-130017. PMID:24531152 doi:https://dx.doi.org/10.3233/JAD-130017
- ↑ Hirose M, Kuroda Y, Murata E. NGF/TrkA Signaling as a Therapeutic Target for Pain. Pain Pract. 2016 Feb;16(2):175-82. doi: 10.1111/papr.12342. Epub 2015 Aug 27. PMID:26452158 doi:https://dx.doi.org/10.1111/papr.12342
- ↑ Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC. Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron. 2007 Jan 4;53(1):25-38. PMID:17196528 doi:10.1016/j.neuron.2006.09.034
- ↑ Wiesmann C, Ultsch MH, Bass SH, de Vos AM. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature. 1999 Sep 9;401(6749):184-8. PMID:10490030 doi:10.1038/43705
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3D structures of high affinity nerve growth factor receptor
Updated on 01-January-2019
{"openlevels":0}
- High affinity nerve growth factor receptor; Domains – nerve growth factor-binding 36-383; transmembrane 410-447; catalytic+juxtamembrane 376-698; kinase 498-796
- 1he7 – hTrkA residues 282-413 – human
- 2n90 – hTrkA transmembrane domain – NMR
- 4crp – hTrkA nerve growth factor-binding domain (mutant) – NMR
- 4f0i, 4gt5 – hTrkA kinase domain
- High affinity nerve growth factor receptor complex
- 5kvt, 5wr7 – hTrkA kinase domain + anticancer drug
- 4aoj, 4pmm, 4pmp, 4pms, 4pmt, 4yne, 4yps, 5h3q, 6dkb, 6dkg, 6dki, 6dkw – hTrkAChoE kinase domain + inhibitor
- 5kmj, 5kmk, 5kml, 5kmm, 5kmn, 5kmo, 6d1y, 6d1z, 6d20, 5i8a, 5jfs, 5jfv, 5jfw, 5jfx, 5kmi, – hTrkAChoE catalytic+juxtamembrane domains 376-698 + inhibitor
- 2ifg – hTrkAChoE nerve growth factor-binding domain + nerve growth factor
References
