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Modeled structure of the 75‐kDa neurotrophin receptor
Author(s) -
Chapman Barbara S.,
Kuntz Irwin D.
Publication year - 1995
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560040905
Subject(s) - receptor , homology modeling , docking (animal) , lymphotoxin , microbiology and biotechnology , ligand (biochemistry) , dimer , neurotrophin , protein structure , chemistry , biology , biophysics , biochemistry , medicine , nursing , organic chemistry , enzyme
Motifs in ligand‐binding domains of the neurotrophin (NTR) and lymphotoxin (TNFR‐I) receptors define a family of receptors that mediates programmed cell death. We have explored relationships of architecture and function in this family through a molecular model of NTR, also called p75NGFR or LANR. Modeling by homology took advantage of four modular subdomains in the crystal structure of TNFR‐1 that also occur in NTR. Hypothetical complexes between the model and a ligand structure (for nerve growth factor, NGF) were then examined using docking software. NTR appears to bind in the dimer interface of NGF, making two sets of contacts. NTR subdomains III and IV provide the ligand‐contact surfaces, in contrast to TNFR, in which subdomains II and III contact TNF‐ β . NTR subdomain II appears to have been evolutionarily modified, potentially contributing to an interface between receptor subunits. These and other specific predictions of the model will require experimental confirmation.