A novel CFTR disease-associated mutation causes addition of an extra N-linked oligosaccharide

Marcus M. Hämmerle, Andrei A. Aleksandrov, Xiu Bao Chang, John R. Riordan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We have examined the influence of a novel missense mutation in the fourth extracytoplasmic loop (EL4) of CFTR detected in a patient with cystic fibrosis. This substitution (T908N) creates a consensus sequence (N X S/T) for addition of an N-linked oligosaccharide chain near the C-terminal end of EL4. Oligosaccharyl transferase generally does not have access to this consensus sequence if it is closer than about twelve amino acids from the membrane. However, the T908N site is used, even though it is within four residues of the predicted membrane interface and the oligosaccharide chain added binds calnexin, a resident chaperone of the ER membrane. The chloride channel activity of this variant CFTR is abnormal as evidenced by a reduced rate of 36Cl- efflux and a noisy single channel open state. This may reflect some displacement of the membrane spanning sequence C-terminal of EL4 since it contains residues influencing the ion pore.

Original languageEnglish (US)
Pages (from-to)807-813
Number of pages7
JournalGlycoconjugate Journal
Volume17
Issue number11
DOIs
StatePublished - Jan 1 2000

Keywords

  • CFTR
  • Glycosylation
  • Ion channel
  • Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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