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

Autor:	M M, Hämmerle, A A, Aleksandrov, X B, Chang, J R, Riordan
Rok vydání:	2001
Předmět:	Models Molecular Cystic Fibrosis Calnexin Calcium-Binding Proteins Molecular Sequence Data Mutation Cystic Fibrosis Transmembrane Conductance Regulator Humans Oligosaccharides Amino Acid Sequence Protein Processing Post-Translational Protein Binding
Zdroj:	Glycoconjugate journal. 17(11)
ISSN:	0282-0080
Popis:	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 (36)Cl(-) 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::ef25c74580be764c6a6638bcdd0b0a7c https://pubmed.ncbi.nlm.nih.gov/11443282 Zobrazit plný text záznamu Full text from SpringerLink