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.
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1 June 2006
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May 30 2006
Statistical Limits to the Identification of Ion Channel Domains by Sequence Similarity
Anthony A. Fodor,
Anthony A. Fodor
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
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Richard W. Aldrich
Richard W. Aldrich
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
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Anthony A. Fodor
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
Richard W. Aldrich
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
Correspondence to Anthony Fodor: [email protected]
A. Fodor's present address is Department of Bioinformatics/Computer Science, University of North Carolina, Charlotte, 9201 University City Blvd., Charlotte, NC 28223.
R. Aldrich's present address is Section of Neurobiology, University of Texas at Austin, Austin, TX 78712.
Abbreviations used in this paper: BK, large conductance calcium-activated potassium; HMM, hidden Markov model; RCK, regulator of potassium conductance; SCOP, structural classification of proteins.
Received:
September 30 2005
Accepted:
May 15 2006
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2006
J Gen Physiol (2006) 127 (6): 755–766.
Article history
Received:
September 30 2005
Accepted:
May 15 2006
Citation
Anthony A. Fodor, Richard W. Aldrich; Statistical Limits to the Identification of Ion Channel Domains by Sequence Similarity . J Gen Physiol 1 June 2006; 127 (6): 755–766. doi: https://doi.org/10.1085/jgp.200509419
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