Unknown

Dataset Information

0

Molecular Basis for Immunity Protein Recognition of a Type VII Secretion System Exported Antibacterial Toxin.


ABSTRACT: Gram-positive bacteria deploy the type VII secretion system (T7SS) to facilitate interactions between eukaryotic and prokaryotic cells. In recent work, we identified the TelC protein from Streptococcus intermedius as a T7SS-exported lipid II phosphatase that mediates interbacterial competition. TelC exerts toxicity in the inner wall zone of Gram-positive bacteria; however, intercellular intoxication of sister cells does not occur because they express the TipC immunity protein. In the present study, we sought to characterize the molecular basis of self-protection by TipC. Using sub-cellular localization and protease protection assays, we show that TipC is a membrane protein with an N-terminal transmembrane segment and a C-terminal TelC-inhibitory domain that protrudes into the inner wall zone. The 1.9-Å X-ray crystal structure of a non-protective TipC paralogue reveals that the soluble domain of TipC proteins adopts a crescent-shaped fold that is composed of three ?-helices and a seven-stranded ?-sheet. Subsequent homology-guided mutagenesis demonstrates that a concave surface formed by the predicted ?-sheet of TipC is required for both its interaction with TelC and its TelC-inhibitory activity. S. intermedius cells lacking the tipC gene are susceptible to growth inhibition by TelC delivered between cells; however, we find that the growth of this strain is unaffected by endogenous or overexpressed TelC, although the toxin accumulates in culture supernatants. Together, these data indicate that the TelC-inhibitory activity of TipC is only required for intercellularly transferred TelC and that the T7SS apparatus transports TelC across the cell envelope in a single step, bypassing the cellular compartment in which it exerts toxicity en route.

SUBMITTER: Klein TA 

PROVIDER: S-EPMC6193138 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Molecular Basis for Immunity Protein Recognition of a Type VII Secretion System Exported Antibacterial Toxin.

Klein Timothy A TA   Pazos Manuel M   Surette Michael G MG   Vollmer Waldemar W   Whitney John C JC  

Journal of molecular biology 20180905 21


Gram-positive bacteria deploy the type VII secretion system (T7SS) to facilitate interactions between eukaryotic and prokaryotic cells. In recent work, we identified the TelC protein from Streptococcus intermedius as a T7SS-exported lipid II phosphatase that mediates interbacterial competition. TelC exerts toxicity in the inner wall zone of Gram-positive bacteria; however, intercellular intoxication of sister cells does not occur because they express the TipC immunity protein. In the present stu  ...[more]

Similar Datasets

| S-EPMC8740702 | biostudies-literature
| S-EPMC6954902 | biostudies-literature
| S-EPMC5325307 | biostudies-literature
| S-EPMC3325213 | biostudies-literature
| S-EPMC6914368 | biostudies-literature
| S-EPMC9600267 | biostudies-literature
| S-EPMC7456083 | biostudies-literature
| S-EPMC2906315 | biostudies-literature
| S-EPMC7773334 | biostudies-literature
| S-EPMC6056853 | biostudies-literature