Activity-associated effect of LDL receptor missense variants located in the cysteine-rich repeats.
Atherosclerosis
; 238(2): 304-12, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25545329
ABSTRACT
BACKGROUND:
The LDL receptor (LDLR) is a Class I transmembrane protein critical for the clearance of cholesterol-containing lipoprotein particles. The N-terminal domain of the LDLR harbours the ligand-binding domain consisting of seven cysteine-rich repeats of approximately 40 amino acids each. Mutations in the LDLR binding domain may result in loss of receptor activity leading to familial hypercholesterolemia (FH). In this study the activity of six mutations located in the cysteine-rich repeats of the LDLR has been investigated.METHODS:
CHO-ldlA7 transfected cells with six different LDLR mutations have been used to analyse in vitro LDLR expression, lipoprotein binding and uptake. Immunoblotting of cell extracts, flow cytometry and confocal microscopy have been performed to determine the effects of these mutations. In silico analysis was also performed to predict the mutation effect. RESULTS ANDCONCLUSION:
From the six mutations, p.Arg257Trp turned out to be a non-pathogenic LDLR variant whereas p.Cys116Arg, p.Asp168Asn, p.Asp172Asn, p.Arg300Gly and p.Asp301Gly were classified as binding-defective LDLR variants whose effect is not as severe as null allele mutations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Mutação de Sentido Incorreto
/
Hiperlipoproteinemia Tipo II
/
Lipoproteínas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article