As the most abundant hunters on Earth, bacteriophages evolved umpteen range of tools to find and bind bacteria, hijack their metabolism to multiply, and lyse the host for progeny release. Studies of every aspect of the phage infection cycle provided us with understanding of fundamentals of living systems and with tools for technological advancement. Relatively slow but persistent spread of antibiotic-resistant bacteria generates demand for diverse antimicrobials. Virosphere seems to be a natural ever-evolving inexhaustible source of such antimicrobials. And yet using bacteria-killing viruses to tackle infections turned out to be not as straightforward as could have been expected.

Little is known about what happens when a phage transits from initial binding of the cell surface to the membrane penetration and genome transfer. A crucial act of decision-making for an individual viral particle remains among the most understudied aspects of viral infection process. Gedankenexperiment approach combined with the fragmented data from a number of experimental systems can help building a convincing model of such a process. Conceivable steps are as follows. Recognition of a specific membrane embedded receptor by a cognate phage receptor-recognition protein, proper orientation of a phage particle on the cell surface, tail opening, trans-membrane and, in many cases, trans-periplasmic channel formation and switch into the genome transfer mode. Nonetheless, the lack of structural data on the subject is considerable, limiting possibilities for quantitative description of infection and phage engineering. One of the reasons for that comes from complexity of host recognition. After all, a phage usually engages several types of specialized appendages - fibers and spikes - into complex interactions with a number of distinct chemical entities on the cell surface before the host recognition reaches irreversible stage and genome transfer begins. Successful host recognition dictates a certain trajectory of binding events none of which can be skipped.

Some phages from the Siphoviridae family provide excellent models for studies of obscured steps of host recognition as they can bypass all the initial and axillary interactions with the cell on the way to the ultimate receptor. If that receptor is sufficiently exposed, the phage can bind it and start infection. Lambda is that type of a phage. It was shown that lambda can infect sensitive Escherichia coli strains though direct binding to the outer membrane protein lamB. One type of tail appendages - central fiber - is necessary and sufficient for lamB recognition and binding. Lambda genome ejection can be triggered with solubilized lamB in vitro in the absence of other cellular components. Lambda ejects its genome into liposomes decorated with lamB recapitulating the chain of events leading to the trans-membrane channel formation in vivo. Studying transition from initial to irreversible host binding at earliest steps of lambda infection benefits from clarity of a radically disentangled system while preserving the possibility to reveal complete mechanics of a key viral decision-making event.

We report a near-atomic resolution structure of bacteriophage lambda tail and its transformation upon receptor binding. The structural analysis suggests limited role of the portal assembly in genome release and evolving of a greater tail-tip autonomy in genome ejection decision making.