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'''NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR''' | '''NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR''' | ||
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[[Category: Vos, A M.De.]] | [[Category: Vos, A M.De.]] | ||
[[Category: Wiesmann, C.]] | [[Category: Wiesmann, C.]] | ||
[[Category: | [[Category: Complex]] | ||
[[Category: | [[Category: Cysteine knot]] | ||
[[Category: | [[Category: Immunoglobulin like domain]] | ||
[[Category: | [[Category: Nerve growth factor]] | ||
[[Category: | [[Category: Trka receptor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:14:44 2008'' | |||
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Revision as of 14:14, 3 May 2008
NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR
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.
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 Page seeded by OCA on Sat May 3 14:14:44 2008