Membrane topology of CLN3, the protein underlying Batten disease

FEBS Letters

Foster, Brian J¹  Xia, Haibin¹  Mao, Qinwen¹  Davidson, Beverly L¹ 

[1] Program in Molecular Biology and Departments of Internal Medicine, Neurology, Physiology, University of Iowa College of Medicine, Iowa City, IA 52242, USA

关键词: Batten disease;    Membrane-spanning domain;    Protein topology;   

DOI  :  10.1016/S0014-5793(03)00284-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Juvenile neuronal ceroid lipofuscinosis, or Batten disease, is an autosomal recessive disorder characterized by progressive loss of motor and cognitive functions, loss of vision, progressively severe seizures, and death. The disease is associated with mutations in the gene CLN3, which encodes a novel 438 amino acid protein, the function of which is currently unknown. Protein secondary structure prediction programs suggest that the CLN3 protein has five to seven membrane-spanning domains (MSDs). To distinguish among a number of hypothetical models for the membrane topology of CLN3 we used in vitro translation of native, Flag epitope-labeled and glycosylation site-mutated CLN3 protein in the presence or absence of canine pancreatic microsomes. These were immunoprecipitated using antibodies specific for Flag or peptide sequences within CLN3 or left untreated. The results indicate that CLN3 contains five MSDs, an extracellular/intraluminal amino-terminus, and a cytoplasmic carboxy-terminus.

【 授权许可】

Unknown