title: Membrane topology of CLN3, the protein underlying Batten disease.
abstract: 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.
authors.affiliation: Program in Molecular Biology and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Mao
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Foster
authors.forename: Haibin
authors.initials: H
authors.lastname: Xia
authors.forename: Beverly L
authors.initials: BL
authors.lastname: Davidson
mesh_terms: D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000209:etiology; D011233:Precipitin Tests; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins