title: Statistical limits to the identification of ion channel domains by sequence similarity.
abstract: The study of ion channel function is constrained by the availability of structures for only a small number of channels. A commonly used bioinformatics technique is to assert, based on sequence similarity, that a domain within a channel of interest has the same structure as a reference domain for which the structure is known. This technique, while useful, is often employed when there is only a slight similarity between the channel of interest and the domain of known structure. In this study, we exploit recent advances in structural genomics to calculate the sequence-based probability of the presence of putative domains in a number of ion channels. We find strong support for the presence of many domains that have been proposed in the literature. For example, eukaryotic and prokaryotic CLC proteins almost certainly share a common structure. A number of proposed domains, however, are not as well supported. In particular, for the COOH terminus of the BK channel we find a number of literature proposed domains for which the assertion of common structure based on common sequence has a nontrivial probability of error.
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, CA 94305, USA. anthony.fodor@gmail.com
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fodor
authors.forename: Richard W
authors.initials: RW
authors.lastname: Aldrich
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000737:chemistry; D030562:Databases, Protein / Q000706:statistics & numerical data; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000737:chemistry*; D051379:Mice; D011237:Predictive Value of Tests; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment / Q000706:statistics & numerical data*; D017386:Sequence Homology, Amino Acid
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels