High affinity nerve growth factor receptor: Difference between revisions
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<StructureSection load=' | <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'> | ||
== Function == | == Function == | ||
'''High affinity nerve growth factor receptor''' (TrkA) is a tyrosine kinase receptor. | '''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]]. | ||
== | == 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; Domains – nerve growth factor-binding 36-383; transmembrane 410-447; catalytic+juxtamembrane 376-698; kinase 498-796 | *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]] – hTrkA residues 282-413 – human<br /> | **[[1he7]] – hTrkA residues 282-413 – human<br /> | ||
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**[[5kvt]], [[5wr7]] – hTrkA kinase domain + anticancer drug<br /> | **[[5kvt]], [[5wr7]] – hTrkA kinase domain + anticancer drug<br /> | ||
**[[4aoj]], [[4pmm]], [[4pmp]], [[4pms]], [[4pmt]], [[4yne]], [[4yps]], [[5h3q]], [[6dkb]], [[6dkg]], [[6dki]], [[6dkw]] – | **[[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 /> | ||
**[[ | **[[8j5w]], [[8j5x]] – hTrkA kinase domain (mutant) + inhibitor<br /> | ||
**[[2ifg]] – | **[[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 /> | |||
}} | }} | ||
