MODELED STRUCTURE OF THE 75-KDA NEUROTROPHIN RECEPTOR

被引:41
作者
CHAPMAN, BS
KUNTZ, ID
机构
[1] University of California, San Francisco, California
关键词
HOMOLOGY MODELING; LIGAND BINDING; NEUROTROPHIN RECEPTOR; NGF; NGFR/TNFR FAMILY; PROTEIN-PROTEIN DOCKING;
D O I
10.1002/pro.5560040905
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-I 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-beta. 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.
引用
收藏
页码:1696 / 1707
页数:12
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