4ZRZ

PlyCB mutant R66E

Summary for 4ZRZ

• Entry DOI: 10.2210/pdb4zrz/pdb
• Related: 4F87 4F88
• Descriptor: PlyCB (2 entities in total)
• Functional Keywords: bacteriocidal, bacteriophage lysin, cell-binding subunit, octameric, cell-wall-cutting, antimicrobial protein, viral protein
• Biological source: Streptococcus phage C1
• Total number of polymer chains: 2
• Total formula weight: 15679.73

Authors

Gallagher, D.T.,Nelson, D.C.,Shen, Y. (deposition date: 2015-05-12, release date: 2016-09-14, Last modification date: 2023-09-27)

Primary citation

Shen, Y.,Barros, M.,Vennemann, T.,Gallagher, D.T.,Yin, Y.,Linden, S.B.,Heselpoth, R.D.,Spencer, D.J.,Donovan, D.M.,Moult, J.,Fischetti, V.A.,Heinrich, F.,Losche, M.,Nelson, D.C.
A bacteriophage endolysin that eliminates intracellular streptococci.
Elife, 5:-, 2016

PubMed Abstract: PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB-PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities.

PubMed: 26978792
DOI: 10.7554/eLife.13152

Experimental method

X-RAY DIFFRACTION (1.72 Å)