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| <StructureSection load='2ifg' size='340' side='right' caption='Glycosylated human TrkA (grey and green) complex with nerve growth factor (yellow and pink) (PDB code [[2ifg]])' scene=''> | | <StructureSection load='2ifg' size='340' side='right' caption='Glycosylated human TrkA (cyan and green) complex with nerve growth factor (yellow and magenta) (PDB code [[2ifg]])' scene='80/805001/Cv/1'> |
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| == Function == | | == Function == |
Revision as of 09:50, 27 December 2018
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Function
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[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
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].
- ↑ 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 27-December-2018
{"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
