1WWW

NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR

Summary for 1WWW

• Entry DOI: 10.2210/pdb1www/pdb
• Descriptor: PROTEIN (NERVE GROWTH FACTOR), PROTEIN (TRKA RECEPTOR) (3 entities in total)
• Functional Keywords: complex, trka receptor, nerve growth factor, cysteine knot, immunoglobulin like domain, nerve growth factor-trka complex complex, nerve growth factor/trka complex
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01138; Cell membrane; Single-pass type I membrane protein (By similarity): P04629
• Total number of polymer chains: 4
• Total formula weight: 49245.74

Authors

Wiesmann, C.,Ultsch, M.H.,De Vos, A.M. (deposition date: 1999-03-12, release date: 1999-09-15, Last modification date: 2024-10-30)

Primary citation

Wiesmann, C.,Ultsch, M.H.,Bass, S.H.,de Vos, A.M.
Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor.
Nature, 401:184-188, 1999

PubMed Abstract: 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.

PubMed: 10490030
DOI: 10.1038/43705

Experimental method

X-RAY DIFFRACTION (2.2 Å)