Structure of Nerve Growth Factor Complexed with the Shared Neurotrophin Receptor p75

Xiao Lin He, K. Christopher Garcia*

*Corresponding author for this work

Research output: Contribution to journalArticle

220 Scopus citations

Abstract

Neurotrophins are secreted growth factors critical for the development and maintenance of the vertebrate nervous system. Neurotrophins activate two types of cell surface receptors, the Trk receptor tyrosine kinases and the shared p75 neurotrophin receptor. We have determined the 2.4 Å crystal structure of the prototypic neurotrophin, nerve growth factor (NGF), complexed with the extracellular domain of p75. Surprisingly, the complex is composed of an NGF homodimer asymmetrically bound to a single p75. p75 binds along the homodimeric interface of NGF, which disables NGF's symmetry-related second p75 binding site through an allosteric conformational change. Thus, neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex.

Original languageEnglish (US)
Pages (from-to)870-875
Number of pages6
JournalScience
Volume304
Issue number5672
DOIs
StatePublished - May 7 2004

ASJC Scopus subject areas

  • General

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