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