Understanding Voltage-gated Sodium Channel Auxiliary Subunits via Bioinformatics
Disciplines
Bioinformatics | Computational Biology | Genomics | Molecular Genetics | Other Ecology and Evolutionary Biology
Abstract (300 words maximum)
Voltage-gated sodium channels are well known to initiate action potentials in electrically excitable cells. Auxiliary subunits for these voltage-gated ion channels diversify the functions of the principal subunit in the capacity of transport kinetics and biogenesis. Our goal has been to elucidate the relationship between function and evolution on a structural basis for each of these families. Three families of sodium channel auxiliary subunits have been included in our study: beta1 (SCN1B)/beta3 (SCN3B), beta2 (SCN2B)/beta4(SCN4B), and TipE. All beta subunits have been shown to have a role in modulating the gating kinetics of voltage-gated sodium channels. Previous findings were expanded after BLAST searches to reveal over 150 new homologues of beta1 and beta3 subunits, which was a significant increase from eight sequences as reported before. Furthermore, secondary structural similarity between beta1/beta3 and beta2/beta4 was observable without established similarity on their primary sequences. Kyte-Doolittle hydropathy plots demonstrated similarities in topology between all beta subunits to indicate the common structural feature of one transmembrane helix. In addition to ones previously reported from insects, we recently discovered homologous sequences of the TipE family from small crustaceans. Sequence similarities were demonstrated by multiple sequence alignments from each family. Phylogenetic trees were derived from multiple sequence alignments to infer evolutionary relationships among these potential homologues. Mutations that cause disruptions in observed disulfide bonds may result in epilepsy syndrome. In addition to sequence-level conservations, our results will show an expanded view on the phylogenetic relationships among members of each auxiliary subunit family.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Tsai-Tien Tseng
Understanding Voltage-gated Sodium Channel Auxiliary Subunits via Bioinformatics
Voltage-gated sodium channels are well known to initiate action potentials in electrically excitable cells. Auxiliary subunits for these voltage-gated ion channels diversify the functions of the principal subunit in the capacity of transport kinetics and biogenesis. Our goal has been to elucidate the relationship between function and evolution on a structural basis for each of these families. Three families of sodium channel auxiliary subunits have been included in our study: beta1 (SCN1B)/beta3 (SCN3B), beta2 (SCN2B)/beta4(SCN4B), and TipE. All beta subunits have been shown to have a role in modulating the gating kinetics of voltage-gated sodium channels. Previous findings were expanded after BLAST searches to reveal over 150 new homologues of beta1 and beta3 subunits, which was a significant increase from eight sequences as reported before. Furthermore, secondary structural similarity between beta1/beta3 and beta2/beta4 was observable without established similarity on their primary sequences. Kyte-Doolittle hydropathy plots demonstrated similarities in topology between all beta subunits to indicate the common structural feature of one transmembrane helix. In addition to ones previously reported from insects, we recently discovered homologous sequences of the TipE family from small crustaceans. Sequence similarities were demonstrated by multiple sequence alignments from each family. Phylogenetic trees were derived from multiple sequence alignments to infer evolutionary relationships among these potential homologues. Mutations that cause disruptions in observed disulfide bonds may result in epilepsy syndrome. In addition to sequence-level conservations, our results will show an expanded view on the phylogenetic relationships among members of each auxiliary subunit family.