Molecular characterization of voltage-gated calcium channel β-subunits of Clonorchis sinensis

The voltage-gated Ca2+ channel β-subunit is a member of the membrane-associated guanylate kinase family and modulates kinetic properties of the Ca2+ channels, such as their voltage-dependent activation and inactivation rates. Two cDNA clones were identified to encode each β-subunit isotype of the voltage-gated Ca2+ channel of Clonorchis sinensis, CsCavβ1 and CsCavβ2, which consist of 606 and 887 amino acids, respectively. CsCavβ1 was found to be similar to the β-subunit containing two conserved serine residues that constitute the consensus protein kinase C phosphorylation site in the β-interaction domain (BID). CsCavβ2 had cysteine and alanine residues instead of the two serine residues conserved in BID and was homologous to variant β-subunit of Schistosoma mansoni and Schistosoma japonicum. CsCavβ1 and CsCavβ2 were almost equally expressed in the adults and metacercariae, but were more expressed in adult C. sinensis than in metacercariae. Collectively, our findings suggest that substitution of the two serine residues in BID of CsCavβ2 may render C. sinensis sensitive to praziquantel.