Anchoring surface proteins to the bacterial cell wall by sortase enzymes: how it started and what we know now

• Published in: Current opinion in microbiology 2021-04, Vol.60, p.73-79
• Main Authors: Bhat, Aadil H, Nguyen, Minh Tan, Das, Asis, Ton-That, Hung
• Format: Article
• Language: English
• Subjects: Aminoacyltransferases - genetics; Bacterial Proteins - genetics; Cell Wall; Cysteine Endopeptidases - genetics; Membrane Proteins
• ISSN: 1369-5274; 1879-0364
• DOI: 10.1016/j.mib.2021.01.013

•Sortase covalently links surface proteins and pili with the CWSS to peptidoglycan.•Unfolded precursors of surface proteins and pili are folded non oxidatively or oxidatively.•Sortase enzymes contain structural elements that determine substrate specificity.•The CWSS remnant serves as a ligand for an intramembrane sensory circuit. In Gram-positive bacteria, the peptidoglycan serves as a placeholder for surface display of a unique class of monomeric and polymeric proteins, or pili — the precursors of which harbor a cell wall sorting signal with LPXTG motif that is recognized by a conserved transpeptidase enzyme called sortase. Since this original discovery over two decades ago, extensive genetic, biochemical and structural studies have illuminated the basic mechanisms of sortase-mediated cell wall anchoring of surface proteins and pili. We now know how LPXTG-containing surface proteins are folded post-translocationally, how sortase enzymes recognize substrates, and how a remnant of the cell wall sorting signal modulates intramembrane signaling. In this review, we will highlight new findings from a few model experimental paradigms and present future prospects for the field.