Signal peptidase I: cleaving the way to mature proteins.
Signal peptidase I (SPase I) is critical for the release of translocated preproteins from the membrane as they are transported from a cytoplasmic site of synthesis to extracytoplasmic locations. These proteins are synthesized with an amino-terminal extension, the signal sequence, which directs the preprotein to the Sec- or Tat-translocation pathway. Recent evidence indicates that the SPase I cleaves preproteins as they emerge from either pathway, though the steps involved are unclear. Now that the structure of many translocation pathway components has been elucidated, it is critical to determine how these components work in concert to support protein translocation and cleavage. Molecular modeling and NMR studies have provided insight on how the preprotein docks on SPase I in preparation for cleavage. This is a key area for future work since SPase I enzymes in a variety of species have now been identified and the inhibition of these enzymes by antibiotics is being pursued. The eubacterial SPase I is essential for cell viability and belongs to a unique group of serine endoproteases which utilize a Ser-Lys catalytic dyad instead of the prototypical Ser-His-Asp triad used by eukaryotes. As such, SPase I is a desirable antimicrobial target. Advances in our understanding of how the preprotein interfaces with SPase I during the final stages of translocation will facilitate future development of inhibitors that display a high efficacy against SPase I function.
Department of Pharmaceutical Sciences, The University of Connecticut, Storrs, CT 06269, USA.
Sarah M
SM
Auclair
Meera K
MK
Bhanu
Debra A
DA
Kendall
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D021381:Protein Transport; D012697:Serine Endopeptidases / Q000378:metabolism*
D001426:Bacterial Proteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D012697:Serine Endopeptidases; C026515:type I signal peptidase