The N-end rule adaptor protein ClpS from Plasmodium falciparum exhibits broad substrate specificity.

The N-end rule is a conserved protein degradation pathway that relates the metabolic stability of a protein to the identity of its N-terminal residue. Proteins bearing a destabilising N-terminal residue (N-degron) are recognised by specialised components of the pathway (N-recognins) and degraded by cellular proteases. In bacteria, the N-recognin ClpS is responsible for the specific recognition of proteins bearing an N-terminal destabilising residue such as leucine, phenylalanine, tyrosine or tryptophan. In this study, we show that the putative apicoplast N-recognin from Plasmodium falciparum (PfClpS), in contrast to its bacterial homologues, exhibits an expanded substrate specificity that includes recognition of the branched chain amino acid isoleucine.