High affinity nerve growth factor receptor: Difference between revisions

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New page: <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> == Function == '''High affinity nerve growth factor receptor''' (TrkA) is a tyrosine...
 
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<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/2'>
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>


== Function ==
== 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<ref>PMID:9759973</ref>.
'''High affinity nerve growth factor receptor''' (TrkA) is a [[tyrosine kinase receptor|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>. See also [[Neurotrophin]].  


== Disease ==
== Relevance ==


== Relevance ==
TrkA has a role in the pathogenesis of psoriasis and its inhibitors are studied in the development of novel therapeutics for the disease<ref name="TrkA"/>.  TrkA inhibition may be a novel therapeutic approach to Alzheimer disease<ref>PMID:24531152</ref> and a new method to treat intractable pain<ref>PMID:26452158</ref>.


== Structural highlights ==
== Structural highlights ==


<scene name='80/805001/Cv/4'>Structure of Nerve Growth Factor Complexed with the Extracellular Domain of TrkA</scene>. An <scene name='80/805001/Cv/7'>Arg residue</scene>, 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<ref>PMID:17196528</ref>, <ref>PMID:10490030</ref>. <scene name='80/805001/Cv/6'>All interactions between TrkA chain A and NGF</scene>.


</StructureSection>
</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
{{#tree:id=OrganizedByTopic|openlevels=0|


*High affinity nerve growth factor receptor
*High affinity nerve growth factor receptor; Domains – nerve growth factor-binding 36-383; D5 – 281-382; transmembrane 410-447; catalytic+juxtamembrane  376-698; kinase 498-796


**[[1he7]] – hTrkAChoE 282-413 – human<br />
**[[1he7]] – hTrkA residues 282-413 – human<br />
**[[2n90]] – hTrkAChoE transmembrane domain 410-447 – NMR<br />
**[[2n90]] – hTrkA transmembrane domain – NMR<br />
**[[4crp]] – hTrkAChoE nerve growth factor-binding domain (mutant) 36-383 – NMR<br />
**[[4crp]] – hTrkA nerve growth factor-binding domain (mutant) – NMR<br />
**[[4f0i]], [[4gt5]] – hTrkAChoE kinase domain 498-796 <br />
**[[4f0i]], [[4gt5]] – hTrkA kinase domain <br />


*High affinity nerve growth factor receptor complex
*High affinity nerve growth factor receptor complex


**[[5kvt]], [[5wr7]] – hTrkAChoE kinase domain 498-796 + anticancer drug<br />
**[[5kvt]], [[5wr7]] – hTrkA kinase domain + anticancer drug<br />
**[[4aoj]], [[4pmm]], [[4pmp]], [[4pms]], [[4pmt]], [[4yne]], [[4yps]], [[5h3q]], [[6dkb]], [[6dkg]], [[6dki]], [[6dkw]] – hTrkAChoE kinase domain + inhibitor<br />
**[[4aoj]], [[4pmm]], [[4pmp]], [[4pms]], [[4pmt]], [[4yne]], [[4yps]], [[5h3q]], [[6dkb]], [[6dkg]], [[6dki]], [[6dkw]], [[6iqn]], [[6j5l]], [[6npt]], [[6nsp]], [[6nss]], [[6pl1]], [[6pl2]], [[6pl3]], [[6pl4]], [[7xaf]], [[7xbi]], [[8j61]], [[8j63]] – hTrkA kinase domain + inhibitor<br />
**[[5kmj]], [[5kmk]], [[5kml]], [[5kmm]], [[5kmn]], [[5kmo]], [[6d1y]], [[6d1z]], [[6d20]], [[5i8a]], [[5jfs]], [[5jfv]], [[5jfw]], [[5jfx]], [[5kmi]], – hTrkAChoE catalytic+juxtamembrane domains 376-698 + inhibitor <br />
**[[8j5w]], [[8j5x]] – hTrkA kinase domain (mutant) + inhibitor<br />
**[[2ifg]] – hTrkAChoE nerve growth factor-binding domain + nerve growth factor <br />
**[[5i8a]], [[5jfs]], [[5jfv]], [[5jfw]], [[5jfx]], [[5kmj]], [[5kmk]], [[5kml]], [[5kmm]], [[5kmn]], [[5kmo]], [[6d1y]], [[6d1z]], [[6d20]], [[6pma]], [[6pmb]], [[6pmc]], [[6pme]] – hTrkA catalytic+juxtamembrane domains + inhibitor <br />
**[[2ifg]] – hTrkA nerve growth factor-binding domain + nerve growth factor <br />
**[[7n3t]] – hTrkA nerve growth factor-binding domain + TrkA-binding miniprotein<br />
**[[8ytd]], [[8yte]] – hTrkA D5 domain + cyclic peptide<br />
 
}}
}}



Latest revision as of 07:01, 26 August 2025

Glycosylated human TrkA (cyan and green) complex with nerve growth factor (yellow and magenta) (PDB code 2ifg)

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3D structures of high affinity nerve growth factor receptor

Updated on 26-August-2025

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky