2IFG

Structure of the extracellular segment of human TRKA in complex with nerve growth factor

Summary for 2IFG

• Entry DOI: 10.2210/pdb2ifg/pdb
• Descriptor: High affinity nerve growth factor receptor, Beta-nerve growth factor, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: trk, trka, ngf, nerve growth factor, receptor-ligand complex, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 109542.64

Authors

He, X.,Garcia, K.C. (deposition date: 2006-09-20, release date: 2007-02-13, Last modification date: 2024-11-13)

Primary citation

Wehrman, T.,He, X.,Raab, B.,Dukipatti, A.,Blau, H.,Garcia, K.C.
Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors.
Neuron, 53:25-38, 2007

PubMed 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.

PubMed: 17196528
DOI: 10.1016/j.neuron.2006.09.034

Experimental method

X-RAY DIFFRACTION (3.4 Å)