6pxe | pdb_00006pxe
Crystal structure of the complex between periplasmic domains of antiholin RI and holin T from T4 phage, in P21
Structural highlights
Function[ANTIH_BPT4] Involved in lysis inhibition. Interacts with and inhibits the holin thereby delaying the host cell lysis timing. Lysis inhibition is imposed when a cell infected by a T4-like virus is superinfected by new incoming viruses. This is probably due to the capsid content of the new phage being released in the periplasm because of blockage of entry due to superinfection exclusion. These periplasmically released viral proteins must somehow activate the periplasmic antiholin, which in turn will block the holin multimerization.[HAMAP-Rule:MF_04105][1] [2] [3] [A0A2U8QQK7_9CAUD] Accumulates harmlessly in the cytoplasmic membrane until it reaches a critical concentration that triggers the formation of micron-scale pores (holes) causing host cell membrane disruption and endolysin escape into the periplasmic space. Determines the precise timing of host cell lysis. Participates with the endolysin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles from the host cell.[HAMAP-Rule:MF_04104] Publication Abstract from PubMedOptimal phage propagation depends on the regulation of the lysis of the infected host cell. In T4 phage infection, lysis occurs when the holin protein (T) forms lesions in the host membrane. However, the lethal function of T can be blocked by an antiholin (RI) during lysis inhibition (LIN). LIN sets if the infected cell undergoes superinfection, then the lysis is delayed until host/phage ratio becomes more favorable for the release of progeny. It has been thought that a signal derived from the superinfection is required to activate RI. Here we report structures that suggest a radically different model in which RI binds to T irrespective of superinfection, causing it to accumulate in a membrane as heterotetrameric 2RI-2T complex. Moreover, we show the complex binds non-specifically to DNA, suggesting that the gDNA from the superinfecting phage serves as the LIN signal and that stabilization of the complex by DNA binding is what defines LIN. Finally, we show that soluble domain of free RI crystallizes in a domain-swapped homotetramer, which likely works as a sink for RI molecules released from the RI-T complex to ensure efficient lysis. These results constitute the first structural basis and a new model not only for the historic LIN phenomenon but also for the temporal regulation of phage lysis in general. The Structural Basis of T4 Phage Lysis Control: DNA as the Signal for Lysis Inhibition.,Krieger I, Kuznetsov V, Chang JY, Zhang J, Moussa S, Young R, Sacchettini JC J Mol Biol. 2020 Jun 17. pii: S0022-2836(20)30409-5. doi:, 10.1016/j.jmb.2020.06.013. PMID:32562709[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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