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NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR
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OverviewOverview
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. 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 (TrkA-d5 domain), is necessary and sufficient for NGF binding. Here we present the crystal, structure of human NGF in complex with human TrkA-d5 at 2.2 A resolution., The ligand-receptor interface consists of two patches of similar size. One, patch involves the central beta-sheet that forms the core of the, homodimeric NGF molecule and the loops at the carboxy-terminal pole of, TrkA-d5. The second patch comprises the amino-terminal residues of NGF, which adopt a helical conformation upon complex formation, packing against, the 'ABED' sheet of TrkA-d5. The structure is consistent with results from, mutagenesis experiments for all neurotrophins, and indicates that the, first patch may constitute a conserved binding motif for all family, members, whereas the second patch is specific for the interaction between, NGF and TrkA.
DiseaseDisease
Known diseases associated with this structure: Insensitivity to pain, congenital, with anhidrosis OMIM:[191315], Medullary thyroid carcinoma, familial OMIM:[191315], Neuropathy, hereditary sensory and autonomic, type V OMIM:[162030]
About this StructureAbout this Structure
1WWW is a Protein complex structure of sequences from Homo sapiens. The following page contains interesting information on the relation of 1WWW with [Neurotrophins]. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor., Wiesmann C, Ultsch MH, Bass SH, de Vos AM, Nature. 1999 Sep 9;401(6749):184-8. PMID:10490030
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