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Atomic model of a bacteriophage-derived cell wall binding module in complex with Listeria wall teichoic acids

AuthorsMartin, R.; Menéndez, M; Cañada, F. Javier ; Shen, Y; Julian-Rodero, A; Prunotto, A; Dunne, M; Bulous, S.; Taylor, NM; Sumrall, E; Eugster, MR; Gerber, B; Leiman, P; Dal Perero, M; Loessner, MJ; Kalograiaki, I
Issue Date6-Nov-2018
CitationThe 2nd International Symposium on Antimicrobial Hydrolytic Enzymes (2018)
AbstractCells in all kingdoms are decorated by glycans of singular and diverse characteristics. Targeted glycan recognition is an initial key step for a great variety of biological processes. Bacterial and bacteriophage-encoded SH3 (Src homology 3) domain is known as conserved cell wall-binding modules mediating cell wall synthesis and bacterial lysis. Previously, we reported that three phage-encoded endolysins (termed CBD500, CBDP35 and CBD025) feature SH3-like fold and exhibit distinct binding patterns that correlate with structural variations in wall teichoic acids (WTAs) of Listeria, their target bacteria. However, the molecular and structural mechanisms underlying SH3-WTA interaction remain elusive. Here, we investigated how CBD500 recognizes specific carbohydrate moieties displayed on the bacterial surface. We disclose the relevant structural modifications of WTA polymers to the binding by genetic deletion, fluorescence microscopy and surface plasmon resonance analysis. Saturation Transfer Difference (STD)-NMR further substantiates that O-acetylation and additional glycosylation of the GlcNAc unit determine the binding specificity. The crystal structure of CBD500, determined by X-ray crystallography and complemented with molecular docking anddynamics simulations, allowed us to propose key residues that form a binding groove. Phe175, Trp 198, Trp242, Asn248, Ser249 and Gly250 mediate WTA recognition by CBD500 through hydrogen bonding and hydrophobic interactions, as validated by structure-guided mutagenesis and isothermal titration calorimetry. Our work reveals the previously unknown recognition mechanism between CBD500 and the native WTA polymers, thus guiding further studies on structure-function relationship of SH3-glycan complex as well as supporting the potential use of endolysins as novel antimicrobials.
DescriptionThe 2nd International Symposium on Antimicrobial Hydrolytic Enzymes. Rockefeller University, 6-8 of November, 2018. New York (USA) .-https://www.thelysinmeeting.com/
Appears in Collections:(CIB) Comunicaciones congresos
(IQFR) Comunicaciones congresos
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