2ifg
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Nerve growth factor engages two structurally distinct transmembrane | + | Nerve growth factor engages two structurally distinct transmembrane receptors, TrkA and p75, which have been proposed to create a "high-affinity" NGF binding site through formation of a ternary TrkA/NGF/p75 complex. To define a structural basis for the high-affinity site, we have determined the three-dimensional structure of a complete extracellular domain of TrkA complexed with NGF. The complex reveals a crab-shaped homodimeric TrkA structure, but a mechanism for p75 coordination is not obvious. We investigated the heterodimerization of membrane-bound TrkA and p75, on intact mammalian cells, using a beta-gal protein-protein interaction system. We find that NGF dimerizes TrkA and that p75 exists on the cell surface as a preformed oligomer that is not dissociated by NGF. We find no evidence for a direct TrkA/p75 interaction. We propose that TrkA and p75 likely communicate through convergence of downstream signaling pathways and/or shared adaptor molecules, rather than through direct extracellular interactions. |
==Disease== | ==Disease== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
| - | [[Category: Garcia, K | + | [[Category: Garcia, K C.]] |
[[Category: He, X.]] | [[Category: He, X.]] | ||
[[Category: nerve growth factor]] | [[Category: nerve growth factor]] | ||
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[[Category: trka]] | [[Category: trka]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:52:12 2008'' |
Revision as of 15:52, 21 February 2008
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Structure of the extracellular segment of human TRKA in complex with nerve growth factor
Contents |
Overview
Nerve growth factor engages two structurally distinct transmembrane receptors, TrkA and p75, which have been proposed to create a "high-affinity" NGF binding site through formation of a ternary TrkA/NGF/p75 complex. To define a structural basis for the high-affinity site, we have determined the three-dimensional structure of a complete extracellular domain of TrkA complexed with NGF. The complex reveals a crab-shaped homodimeric TrkA structure, but a mechanism for p75 coordination is not obvious. We investigated the heterodimerization of membrane-bound TrkA and p75, on intact mammalian cells, using a beta-gal protein-protein interaction system. We find that NGF dimerizes TrkA and that p75 exists on the cell surface as a preformed oligomer that is not dissociated by NGF. We find no evidence for a direct TrkA/p75 interaction. We propose that TrkA and p75 likely communicate through convergence of downstream signaling pathways and/or shared adaptor molecules, rather than through direct extracellular interactions.
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
2IFG is a Protein complex structure of sequences from Homo sapiens. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
Reference
Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors., Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC, Neuron. 2007 Jan 4;53(1):25-38. PMID:17196528
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