A Conserved Signal-Peptidase Antagonist Modulates Membrane Homeostasis of Actinobacterial Sortase Critical for Surface Morphogenesis

Authors

Nicholas A Ramirez
Chenggang Wu
Chungyu Chang
Sara D Siegel
Asis Das
Hung Ton-That

Publication Date

7-12-2022

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abstract

Cell wall anchoring of surface proteins in Gram-positive bacteria requires a sortase enzyme. Here, we unveiled the hitherto unknown function of an evolutionarily conserved small transmembrane protein, named SafA, genetically linked to the housekeeping sortase in Actinobacteria. We show that Actinomyces oris SafA interacts with the housekeeping sortase SrtA via the conserved FPW motif and prevents SrtA cleavage by the signal peptidase LepB2, hence maintaining membrane homeostasis of SrtA. This function is conserved as ectopic expression of SafA from Corynebacterium diphtheriae and Corynebacterium matruchotii in the A. oris safA mutant rescues its defects in cell morphology, pilus assembly, surface protein localization, and polymicrobial interactions. Thus, SafA represents an archetypal antagonist of signal peptidase that modulates surface assembly in Actinobacteria.

Keywords

Actinobacteria, Aminoacyltransferases, Bacterial Proteins, Cysteine Endopeptidases, Homeostasis, Membrane Proteins, Morphogenesis, Serine Endopeptidases

DOI

10.1073/pnas.2203114119

PMID

35787040

PMCID

PMC9282373

PubMedCentral® Posted Date

7-5-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes