title: The transmembrane topology of Batten disease protein CLN3 determined by consensus computational prediction constrained by experimental data.
abstract: The CLN3 gene encodes an integral membrane protein of unknown function. Mutations in CLN3 can cause juvenile neuronal ceroid lipofuscinosis, or Batten disease, an inherited neurodegenerative lysosomal storage disease affecting children. Here, we report a topological study of the CLN3 protein using bioinformatic approaches constrained by experimental data. Our results suggest that CLN3 has a six transmembrane helix topology with cytoplasmic N and C-termini, three large lumenal loops, one of which may contain an amphipathic helix, and one large cytoplasmic loop. Surprisingly, varied topological predictions were made using different subsets of orthologous sequences, highlighting the challenges still remaining for bioinformatics.
authors.affiliation: Bioinformatics Group, Department of Computer Science, University College London, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: Nugent
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001185:Artificial Intelligence; D019295:Computational Biology; D016384:Consensus Sequence; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: C509077:BTN1 protein, S pombe; C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D029702:Schizosaccharomyces pombe Proteins