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Superinfection exclusion strategy of siphophage T5: analysis of the FhuA:Llp complex

Degroux, S.; Deniaud-Vives, C.; Mestdach, E.; Darnault, C.; Le Roy, A.; Mas, C.; Salmon, L.; Herrmann, T.; Breyton, C.

2026-03-28 biophysics
10.64898/2026.03.26.714494 bioRxiv
Show abstract

Superinfection exclusion is a widespread viral mechanism that protects the infected cell from over infection by other, identical or closely related viruses. Shortly after infection by bac-teriophage T5, the bacterium E. coli produces Llp coded by the just injected viral genome. Llp is a small lipoprotein targeted to the inner-leaflet of the host outer-membrane. It binds to FhuA, an outer-membrane iron-ferrichrome transporter, which is T5 receptor at the E. coli cell surface. The interaction between Llp and FhuA prevents any further bacteriophage binding and infection. Here, we determined the RMN structure of Llp and analyse the formation of the FhuA:Llp complex using a wide range of techniques and mutants, both in vivo and in vitro. Interaction of Llp to FhuA is governed by a two-step equilibrium with a strong contribution of induced fit: Llp binding requires remodelling of FhuA periplasmic plug surface, allowing the further large conformational reorganisation of the extracellular loops. Analysis of FhuA mu-tants show the importance of the intertwined interactions between the extracellular loops and the plug in the communication between the periplasmic and the extracellular faces of FhuA.

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