The bacteriophage T4 DNA injection machine
Introduction
Bacterial viruses, or bacteriophages, have developed various strategies through which to infect a susceptible bacterial host. Unlike many other viruses (especially those that infect eukaryotic organisms), most of which enter the host by endocytosis, bacteriophages remain attached to the outer cell surface during infection. A vast majority of phages have evolved to use a special organelle, called a ‘tail’, for host recognition, attachment and genome delivery into the cell [1•]. The tail is attached to the capsid (or head), containing the phage genome, which is packaged in a process that requires energy derived from ATP hydrolysis.
The order of tailed bacteriophages, Caudovirales, contains three families: Myoviridae, Siphoviridae and Podoviridae [1•]. Phages belonging to these three families have contractile, long non-contractile and short non-contractile tails, respectively. Although the tails from all three families are complex macromolecular assemblies, the Myoviridae contractile tails are especially elaborate (Figure 1). For example, more than 20 proteins, each present in multiple copies, comprise the 1200 Å long and 250 Å wide tail of the Myoviridae phage T4 (Table 1) [2]. During infection, the baseplate of the tail attaches the phage particle to the cell surface and undergoes a global conformational change from the ‘hexagonal’ to the ‘star’ conformation. This initiates contraction of the sheath, which drives the tail tube through the cell envelope. Subsequently, the phage genome is passed through the tail tube into the host cytoplasm.
A 12 Å resolution structure of the phage T4 baseplate, obtained by electron cryomicroscopy (cryo-EM), shows that it is a dome-shaped object, approximately 520 Å in diameter and 270 Å high, composed primarily of fibrous proteins [3••]. Crystal structures of six baseplate proteins have been determined by X-ray crystallography and fitted into the cryo-EM map 4., 5.••, 6., 7.•, 8.• (Figure 2). Among these is the tail lysozyme, encoded by gene 5, which is responsible for digesting the intermembrane peptidoglycan layer during infection [5••]. The locations and shapes of other baseplate proteins have also been established, through analysis of the uninterpreted cryo-EM density after fitting the known crystal structures. Based on these structural data and earlier genetic and biochemical results, a mechanism of infection of a Myoviridae phage has been proposed.
Section snippets
Assembly
The protein composition of the tail and the pathway of its assembly have been established (Table 1) 9., 10.; mutants that produce incomplete phage particles have been especially useful in these studies 11., 12., 13.. Assembly of the T4 tail begins with formation of the baseplate, and proceeds with polymerization of the tail tube and the tail sheath. The baseplate is required for initiation of tube assembly. Both the baseplate and the tube are essential for the sheath to adopt the extended
Infection mechanism of a Myoviridae phage T4
Infection is initiated when the long tail fibers interact with the cell surface receptors [lipopolysaccharide molecules or OmpC (surface antigen) proteins]. This interaction is reversible, but when a minimum of three long tail fibers have bound to the host cell receptors, the fibers change their conformation, thereby signaling to the baseplate through gp9 that binding has been successful. Concomitantly, the baseplate is brought into proximity with the cell surface and the short tail fibers
Conclusions
Studies of the bacteriophage T4 baseplate have shown that assembly of large macromolecular complexes can be regulated by sequential interactions of the component proteins but not by the order of gene expression. These experiments have also demonstrated that the multiprotein baseplate, comparable in size and complexity to an average-size icosahedral virus, can undergo large, concerted conformational changes, which coordinate several steps of the phage infection process. Recent structural
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
Acknowledgements
We thank Paul Chipman for providing a cryo-EM photograph of phage T4.
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