The N-end rule pathway

The N-end rule pathway is a ubiquitous protein degradation pathway found in bacteria, yeast and mammals, which relates the half-life of a protein to the identity of its N-terminal residue. Some residues (red) are considered 'stabilizing' when located at the N-terminus of a protein (i.e. the protein is not degraded), while other N-terminal residues (yellow or green) are 'destabilizing' (i.e. trigger rapid turnover of the protein).

Previously, we have shown that the adaptor protein ClpS is essential component of the pathway, required for the recognition (and ClpAP-mediated degradation) of proteins bearing an N-terminal destabilising residue in E. coli (Erbse et al., 2006). We have also identified several natural substrates of this pathway in E. coli (Ninnis et al., 2009) and in collaboration with colleagues in Germany, we have defined to atomic detail, the nature of this elegant interaction between the ClpS and the N-degron (Schuenemann et al., 2009).

Currently we are studying several novel components of the N-end rule pathway, not only in E. coli but also in pathogenic bacteria and mammals.