title: Conserved motifs in voltage-sensing and pore-forming modules of voltage-gated ion channel proteins.
abstract: Voltage-gated ion channels (VGCs) mediate selective diffusion of ions across cell membranes to enable many vital cellular processes. Three-dimensional structure data are lacking for VGC proteins; hence, to better understand their function, there is a need to identify the conserved motifs using sequence analysis methods. In this study, we have used a profile-to-profile alignment method to identify several new conserved motifs specific to each transmembrane segment (TMS) of the voltage-sensing and the pore-forming modules of Ca2+, Na+, and K+ channel subfamilies. For Ca2+ and Na+, the functional theme of motif conservation is similar in all segments while they differ with those of the K+ channel proteins. Nevertheless, the conservation is strikingly similar in the S4 segment of the voltage-sensing module across all subfamilies. In each subfamily and for each TMS, we have identified conserved motifs/residues and correlated their functional significance and disease associations in human, using mutational data from the literature.
authors.affiliation: GenNYsis Center for Excellence in Cancer Genomics and Department of Epidemiology and Biostatistics, State University of New York at Albany, One Discovery Drive, Rensselaer, NY 12144-3456, USA. cguda@albany.edu
authors.forename: Purnima
authors.initials: P
authors.lastname: Guda
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bourne
authors.forename: Chittibabu
authors.initials: C
authors.lastname: Guda
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics*; D008564:Membrane Potentials / Q000235:genetics*; D008969:Molecular Sequence Data; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry; D017421:Sequence Analysis / Q000379:methods*; D013045:Species Specificity
chemical_list: D007473:Ion Channels; D052899:Pore Forming Cytotoxic Proteins