The C5 variant of the butyrylcholinesterase tetramer includes a noncovalently bound 60 kDa lamellipodin fragment

Lawrence M Schopfer, Hervé Delacour, Patrick Masson, Jacqueline Leroy, Eric Krejci, Oksana Lockridge

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE.

Original languageEnglish (US)
Article number1083
JournalMolecules
Volume22
Issue number7
DOIs
StatePublished - Jul 2017

Fingerprint

Butyrylcholinesterase
genes
fragments
muscle relaxants
proteins
body weight
electrophoresis
loci
antibodies
peptides
gels
Genes
Exons
Native Polyacrylamide Gel Electrophoresis
Succinylcholine
Umbilical Cord
Electrophoresis
Antibody Formation
Muscle
Proteins

Keywords

  • Butyrylcholinesterase
  • C5 phenotype
  • Lamellipodin
  • RAPH1
  • Tetramer

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

The C5 variant of the butyrylcholinesterase tetramer includes a noncovalently bound 60 kDa lamellipodin fragment. / Schopfer, Lawrence M; Delacour, Hervé; Masson, Patrick; Leroy, Jacqueline; Krejci, Eric; Lockridge, Oksana.

In: Molecules, Vol. 22, No. 7, 1083, 07.2017.

Research output: Contribution to journalArticle

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abstract = "Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200{\%} higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100{\%} of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90{\%} of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10{\%} of adults with C5 BChE.",
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