Folding anomalies of neuroligin3 caused by a mutation in the α/β-hydrolase fold domain

Antonella De Jaco, Noga Dubi, Davide Comoletti, Palmer Taylor

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Proteins of the α/β-hydrolase fold family share a common structural fold, but perform a diverse set of functions. We have been studying natural mutations occurring in association with congenital disorders in the α/β-hydrolase fold domain of neuroligin (NLGN), butyrylcholinesterase (BChE), acetylcholinesterase (AChE). Starting from the autism-related R451C mutation in the α/β-hydrolase fold domain of NLGN3, we had previously shown that the Arg to Cys substitution is responsible for endoplasmic reticulum (ER) retention of the mutant protein and that a similar trafficking defect is observed when the mutation is inserted at the homologous positions in AChE and BChE. Herein we show further characterization of the R451C mutation in NLGN3 when expressed in HEK-293, and by protease digestion sensitivity, we reveal that the phenotype results from protein misfolding. However, the presence of an extra Cys does not interfere with the formation of disulfide bonds as shown by reaction with PEG-maleimide and estimation of the molecular mass changes. These findings highlight the role of proper protein folding in protein processing and localization.

Original languageEnglish (US)
Pages (from-to)56-58
Number of pages3
JournalChemico-Biological Interactions
Volume187
Issue number1-3
DOIs
StatePublished - Sep 2010

All Science Journal Classification (ASJC) codes

  • Toxicology

Keywords

  • Disulfide bonds
  • Protein folding
  • Protein processing

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