Generation of rationally-designed nerve growth factor (NGF) variants with receptor specificity
Carleton, Laura A. Chakravarthy, Reka van der Sloot, Almer M. Mnich, Katarzyna Serrano, Luis Samali, Afshin Gorman, Adrienne M.
Carleton, Laura A.
Chakravarthy, Reka
van der Sloot, Almer M.
Mnich, Katarzyna
Serrano, Luis
Samali, Afshin
Gorman, Adrienne M.
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Publication Date
2017-11-03
Type
Article
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Citation
Carleton, Laura A., Chakravarthy, Reka, van der Sloot, Almer M., Mnich, Katarzyna, Serrano, Luis, Samali, Afshin, & Gorman, Adrienne M. Generation of rationally-designed nerve growth factor (NGF) variants with receptor specificity. Biochemical and Biophysical Research Communications. doi: https://doi.org/10.1016/j.bbrc.2017.11.003
Abstract
Nerve growth factor (NGF) is the prototypic member of the neurotrophin family and binds two receptors, TrkA and the 75 kDa neurotrophin receptor (p75NTR), through which diverse and sometimes opposing effects are mediated. Using the FoldX protein design algorithm, we generated eight NGF variants with different point mutations predicted to have altered binding to TrkA or p75NTR. Of these, the I31R NGF variant exhibited specific binding to p75NTR. The generation of this NGF variant with selective affinity for p75NTR can be used to enhance understanding of neurotrophin receptor imbalance in diseases and identifies a key targetable residue for the development of small molecules to disrupt binding of NGF to TrkA with potential uses in chronic pain.
Publisher
Elsevier
Publisher DOI
10.1016/j.bbrc.2017.11.003
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Attribution-NonCommercial-NoDerivs 3.0 Ireland