Structural basis of superinfection exclusion by bacteriophage T4 Spackle

Ke Shi, Justin T. Oakland, Fredy Kurniawan, Nicholas H. Moeller, Surajit Banerjee, Hideki Aihara

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13 Scopus citations


A bacterial cell infected with T4 phage rapidly establishes resistance against further infections by the same or closely related T-even-type bacteriophages – a phenomenon called superinfection exclusion. Here we show that one of the T4 early gene products and a periplasmic protein, Spackle, forms a stoichiometric complex with the lysozyme domain of T4 tail spike protein gp5 and potently inhibits its activity. Crystal structure of the Spackle-gp5 lysozyme complex shows that Spackle binds to a horseshoe-shaped basic patch surrounding the oligosaccharide-binding cleft and induces an allosteric conformational change of the active site. In contrast, Spackle does not appreciably inhibit the lysozyme activity of cytoplasmic T4 endolysin responsible for cell lysis to release progeny phage particles at the final step of the lytic cycle. Our work reveals a unique mode of inhibition for lysozymes, a widespread class of enzymes in biology, and provides a mechanistic understanding of the T4 bacteriophage superinfection exclusion.

Original languageEnglish (US)
Article number691
JournalCommunications biology
Issue number1
StatePublished - Oct 19 2020

Bibliographical note

Funding Information:
This work was supported by a grant from the US National Institutes of Health (NIGMS R35-GM118047 to H.A.). This work is based upon research conducted at the North-eastern Collaborative Access Team beamlines, which are funded by the US National Institutes of Health (NIGMS P30 GM124165). The Pilatus 6M detector on 24-ID-C beamline is funded by a NIH-ORIP HEI grant (S10 RR029205). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357, and those of the Minnesota Supercomputing Institute.

Publisher Copyright:
© 2020, The Author(s).


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