The butyrylcholinesterase K-variant shows similar cellular protein turnover and quaternary interaction to the wild-type enzyme

Cibby Varkey Altamirano, Cynthia F. Bartels, Oksana Lockridge

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

A recent study has linked the butyrylcholinesterase (BChE) K-variant and the apolipoprotein ε4 isoform to late-onset Alzheimer's disease. These findings have been controversial and have led us to examine the differences between wild-type and K-variant BChE in enzyme activity, protein stability, and quaternary structure. J-variant BChE (E497V/A539T) was also studied because it is associated with the K-variant mutation. The K-variant mutation (A539T) is located in the C-terminal tetramerization domain. Wild-type, K- variant, and J-variant BChE were expressed in Chinese hamster ovary cells and purified. The purified enzymes had similar binding affinity (K(m)) values and catalytic rates for butyrylthiocholine and benzoylcholine. In pulse-chase studies the K-variant, J-variant, and wildtype BChE were degraded rapidly within the cell, with a half-time of ~1.5 h. Less than 5% of the intracellular BChE was exported. The C-terminal peptide containing the K- variant mutation interacted with itself as strongly as did the wild-type peptide in the yeast two-hybrid system. Both K-variant and wild-type BChE assembled into tetramers in the presence of poly-L-proline or the proline- rich attachment domain of the collagen tail. The native K-variant BChE in serum showed the same proportion of tetramers as the native serum wild-type BChE. We conclude that the K-variant BChE is similar to wild-type BChE in enzyme activity, protein turnover, and tetramer formation.

Original languageEnglish (US)
Pages (from-to)869-877
Number of pages9
JournalJournal of Neurochemistry
Volume74
Issue number2
DOIs
StatePublished - 2000

Keywords

  • Butyrylcholinesterase
  • K-variant
  • Late-onset Alzheimer's disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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