Selenoprotein K and Protein Palmitoylation

Selenoprotein K (SelK) is an endoplasmic reticulum (ER) membrane protein, and its expression is sensitive to dietary selenium levels. A recently described role for SelK as a cofactor in catalyzing protein palmitoylation reactions provides an important link between low dietary selenium intake and suboptimal cellular functions that depend on this selenoprotein for palmitoylation.A recent breakthrough provided insight into the contribution of SelK to calcium (Ca(2+)) flux in immune cells. In particular, SelK is required for palmitoylation of the Ca(2+) channel protein, inositol-1,4,5-triphosphate receptor (IP3R) in the ER membrane. Without this post-translational modification, expression and function of the IP3R is impaired. SelK is required for palmitoylation of another transmembrane protein, CD36, and very likely other proteins. SelK serves as a cofactor during protein palmitoylation by binding to the protein acyltransferase, DHHC6, thereby facilitating addition of the palmitate via a thioester bond to the sulfhydryl group of cysteine residues of target proteins.The association of DHHC6 and SelK is clearly important for immune cell functions and possibly other cell types. The step in the DHHC6 catalyzed S-acylation reaction on which SelK acts remains unclear and possible mechanisms of how the kinetics of the reaction are impacted by SelK binding to DHHC6 are presented here.Uncovering the specific role of SelK in promoting DHHC6 catalyzed protein palmitoylation may open a new line of inquiry into other selenoproteins playing similar roles as cofactors for different enzymatic processes.