COS cell expression studies of P86L, P86R, P480L and P4480Q Hunter's disease-causing mutations

被引:15
作者
Millat, G [1 ]
Froissart, R [1 ]
Cudry, S [1 ]
Bonnet, V [1 ]
Maire, I [1 ]
Bozon, D [1 ]
机构
[1] Hop Debrousse, Ctr Etudes Maladies Metabol, F-69322 Lyon 05, France
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 1998年 / 1406卷 / 02期
关键词
iduronate-2-sulfatase (IDS); mucopolysaccharidosis; Hunter's disease; expression study; lysosome;
D O I
10.1016/S0925-4439(97)00096-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Three missense mutations identified in the IDS gene of our Hunter's disease patients (P86L, P480L and P480Q) and the previously described P86R mutation were expressed in COS cells to evaluate their functional consequence on iduronate-2-sulfatase (IDS) activity and processing. The 86-proline residue belongs to the highly conserved pentapeptide C-X-P-S-R in which cysteine modification to a formylglycine is required for sulfatase activity. The substitution of the 86-proline residue led to a severe mutation as no mature form was targeted to the lysosome in agreement with the severe phenotype observed in patients carrying P86L and P86R mutations. Expression studies with P480L and P480Q mutant cDNAs showed the presence of a small amount of 55 kDa mature form in the lysosomes of transfected COS cells. IDS activity of the P480L and P480Q mutants in cell extracts represents 16.6% and 5.4% of the wild-type, respectively. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:214 / 218
页数:5
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