The bacterial N-end rule pathway: expect the unexpected

Authors

  • D. A. Dougan,

    Corresponding author
    1. Dept. of Biochemistry, Institute for Molecular Science, La Trobe University, Melbourne, Vic. 3086, Australia.
      E-mail d.dougan@latrobe.edu.au; Tel. (+61) 3 9479 3276; Fax (+61) 3 9479 2467.
    Search for more papers by this author
  • K. N. Truscott,

    1. Dept. of Biochemistry, Institute for Molecular Science, La Trobe University, Melbourne, Vic. 3086, Australia.
    Search for more papers by this author
  • K. Zeth

    1. Dept. Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen D-72076, Germany.
    Search for more papers by this author

E-mail d.dougan@latrobe.edu.au; Tel. (+61) 3 9479 3276; Fax (+61) 3 9479 2467.

Summary

The N-end rule pathway is a highly conserved process that operates in many different organisms. It relates the metabolic stability of a protein to its N-terminal amino acid. Consequently, amino acids are described as either ‘stabilizing’ or ‘destabilizing’. Destabilizing residues are organized into three hierarchical levels: primary, secondary, and in eukaryotes – tertiary. Secondary and tertiary destabilizing residues act as signals for the post-translational modification of the target protein, ultimately resulting in the attachment of a primary destabilizing residue to the N-terminus of the protein. Regardless of their origin, proteins containing N-terminal primary destabilizing residues are recognized by a key component of the pathway. In prokaryotes, the recognition component is a specialized adaptor protein, known as ClpS, which delivers target proteins directly to the ClpAP protease for degradation. In contrast, eukaryotes use a family of E3 ligases, known as UBRs, to recognize and ubiquitylate their substrates resulting in their turnover by the 26S proteasome. While the physiological role of the N-end rule pathway is largely understood in eukaryotes, progress on the bacterial pathway has been slow. However, new interest in this area of research has invigorated several recent advances, unlocking some of the secrets of this unique proteolytic pathway in prokaryotes.

Ancillary