PhD candidate Karol Sanches recently published a paper in Proteins: Structure, Function, and Bioinformatics about the heterologous expression of the intrinsic membrane protein of the Caribbean sea anome.

The venoms of sea anemones are rich mixtures of biologically active compounds, some of which have the potential to be developed into novel therapeutics or bioinsecticides. ShK is a 35-residue peptide first isolated from the Caribbean sea anemone Stichodactyla helianthus as a potent blocker of voltage-gated potassium channels. The upregulation of one of these channels, K_V1.3, occurs in many autoimmune and neuroinflammatory diseases, and inhibitors are therefore valuable molecular tools and potential therapeutic leads. The heterologous expression of this intrinsic membrane protein is one of the projects being pursued within the CFBD.

     Since its discovery in a sea anemone, the ShKT domain has been found in numerous other species, including plants, algae, protozoa, other cnidarians (such as hydra and jellyfish), sea urchins, molluscs, sea squirts, fish, nematodes, parasitic worms, snakes, amphibians, birds, and mammals. However, only a small fraction of these ShKT domains has been characterized functionally. Although some peptides display the same ShK-like fold and contain the dyad Lys-Tyr important for K_V1.3 blockade, their function may not be related to potassium channel inhibition. As ShKT domains are highly abundant in nature and their functions are important to define, we investigated whether a combination of structure determination and/or prediction with molecular dynamics (MD) simulations could be useful for predicting activity against voltage-gated potassium channels. We show that weak or absent activity against K_V1.x channels correlated with either a buried or only partially exposed dyad during MD simulations. We anticipate that structure determination in combination with MD simulations may allow the function of new sequences in the ShKT family to be predicted, at least for potassium channel blockers.