Dataset Information

Molecular Mechanisms of the Binding and Specificity of Streptococcus Pneumoniae Sortase C Enzymes for Pilin Subunits.

ABSTRACT: Pili are elongated structures that protrude from bacteria and increase their virulence. The Streptococcus pnuenomae pilus island 1 pili are composed of three subunits, RrgA, RrgB, and RrgC, and are assembled by three class C sortase C (SrtC) enzymes: SrtC-1, SrtC-2, and SrtC-3. Pilin subunits are recognized by SrtC proteins through a pentapeptide sorting signal, and while previous studies have sought to characterize the selectivities of SrtC isoforms for these subunits, the molecular mechanisms underlying these interactions remain unclear. Here, we report a series of molecular dynamics simulations of each SrtC enzyme with the sorting signals of RrgA, RrgB, and RrgC to determine the structural and thermodynamic basis of pilin recognition. Results show that, in accordance with previous studies, both SrtC-1 and SrtC-3 are selective for RrgB, while SrtC-2 is selective for RrgA. This specificity is tuned by the sorting signal binding conformation in which the first two residue sidechains complement hydrophobic residues around the active site, while the third residue projects away from the catalytic triad and makes specific interactions based on its charge and reach. Together, these results provided atomic-scale descriptions of the SrtC substrate selectivity mechanisms and extend the emerging model of pilin construction in S. pnuenomae.

SUBMITTER: Naziga EB

PROVIDER: S-EPMC5640630 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Molecular Mechanisms of the Binding and Specificity of Streptococcus Pneumoniae Sortase C Enzymes for Pilin Subunits.

Naziga Emmanuel B EB Wereszczynski Jeff J

Scientific reports 20171013 1

Pili are elongated structures that protrude from bacteria and increase their virulence. The Streptococcus pnuenomae pilus island 1 pili are composed of three subunits, RrgA, RrgB, and RrgC, and are assembled by three class C sortase C (SrtC) enzymes: SrtC-1, SrtC-2, and SrtC-3. Pilin subunits are recognized by SrtC proteins through a pentapeptide sorting signal, and while previous studies have sought to characterize the selectivities of SrtC isoforms for these subunits, the molecular mechanisms ...[more]

PMID: 29030637

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Project description:Streptococcus pneumoniae (pneumococcus), a major human pathogen, is well known for its adaptation to various host environments. Multiple DNA inversions in the three DNA methyltransferase hsdS genes (hsdSA, hsdSB, and hsdSC) of the colony opacity determinant (cod) locus generate extensive epigenetic and phenotypic diversity. However, it is unclear whether all three hsdS genes are functional and how the inversions mechanistically occur. In this work, our transcriptional analysis revealed active expression of hsdSA but not hsdSB and hsdSC, indicating that hsdSB and hsdSC do not produce functional proteins and instead act as sources for altering the sequence of hsdSA by DNA inversions. Consistent with our previous finding that the hsdS inversions are mediated by three pairs of inverted repeats (IR1, IR2, and IR3), this study showed that the 15-bp IR1 and its upstream sequence are strictly required for the inversion between hsdSA and hsdSB Furthermore, a single tyrosine recombinase PsrA catalyzes the inversions mediated by IR1, IR2, and IR3, based on the dramatic loss of these inversions in the psrA mutant. Surprisingly, PsrA-independent inversions were also detected in the hsdS sequences flanked by the IR2 (298 bp) and IR3 (85 bp) long inverted repeats, which appear to occur spontaneously in the absence of site-specific or RecA-mediated recombination. Because the HsdS subunit is responsible for the sequence specificity of type I restriction modification DNA methyltransferase, these results have revealed that S. pneumoniae varies the methylation patterns of the genome DNA (epigenetic status) by employing multiple mechanisms of DNA inversion in the cod locus.IMPORTANCEStreptococcus pneumoniae is a major pathogen of human infections with the capacity for adaptation to host environments, but the molecular mechanisms behind this phenomenon remain unclear. Previous studies reveal that pneumococcus extends epigenetic and phenotypic diversity by DNA inversions in three methyltransferase hsdS genes of the cod locus. This work revealed that only the hsdS gene that is in the same orientation as hsdM is actively transcribed, but the other two are silent, serving as DNA sources for inversions. While most of the hsdS inversions are catalyzed by PsrA recombinase, the sequences bound by long inverted repeats also undergo inversions via an unknown mechanism. Our results revealed that S. pneumoniae switches the methylation patterns of the genome (epigenetics) by employing multiple mechanisms of DNA inversion.

Dataset Information

Molecular Mechanisms of the Binding and Specificity of Streptococcus Pneumoniae Sortase C Enzymes for Pilin Subunits.

Publications

Molecular Mechanisms of the Binding and Specificity of Streptococcus Pneumoniae Sortase C Enzymes for Pilin Subunits.

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