Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody.
作者： Sonia Covaceuszach , Alberto Cassetta , Petr V. Konarev , Stefania Gonfloni , Rainer Rudolph
DOI: 10.1016/J.JMB.2008.06.008
关键词:
摘要: The anti-nerve growth factor (NGF) monoclonal antibody alphaD11 is a potent antagonist that neutralizes the biological functions of its antigen in vivo. NGF antagonism expected to be highly effective and safe therapeutic approach many pain states. A comprehensive functional structural analysis was carried out, showing ability neutralize binding either tropomyosine receptor kinase (TrkA) or p75 receptors. 3-D structure Fab fragment solved at 1.7 resolution. computational docking model Fab-NGF complex, based on epitope mapping using pool 44 mutants experimentally validated by small-angle X-ray scattering, provided basis for identifying residues involved binding. present study pinpoints loop II an important determinant activity mediated TrkA receptor.
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