1www
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'''NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR'''<br /> | '''NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nerve growth factor (NGF) is involved in a variety of processes involving | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1WWW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1WWW with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb68_1.html Neurotrophins]]. Full crystallographic information is available from [http:// | + | 1WWW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1WWW with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb68_1.html Neurotrophins]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WWW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Neurotrophins]] | [[Category: Neurotrophins]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Ultsch, M | + | [[Category: Ultsch, M H.]] |
| - | [[Category: Vos, A | + | [[Category: Vos, A M.De.]] |
[[Category: Wiesmann, C.]] | [[Category: Wiesmann, C.]] | ||
[[Category: complex]] | [[Category: complex]] | ||
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[[Category: trka receptor]] | [[Category: trka receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:49:00 2008'' |
Revision as of 13:49, 21 February 2008
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NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR
Contents |
Overview
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.
Disease
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 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.
Reference
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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