PMID: 17196528

 

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Title : Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors

Abstract :
  1. 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
  2. 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
  3. The complex reveals a crab-shaped homodimeric TrkA structure, but a mechanism for p75 coordination is not obvious
  4. We investigated the heterodimerization of membrane-bound TrkA and p75 , on intact mammalian cells, using a beta-gal protein-protein interaction system.
  5. We find that NGF dimerizes TrkA and that p75 exists on the cell surface as a preformed oligomer that is not dissociated by NGF
  6. We find no evidence for a direct TrkA / p75 interaction
  7. 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