Bacteriophage, or more commonly 'phage for short, is the name given to viruses that infect bacteria (you can see the schematic diagram of phage T4 on the left). You will have come across the suffix phage in oesophagus or as a prefix in Phagocytosis: it has Greek origins and means to eat. I first came across bacteriophage in 1977 during an
undergraduate lecture by Dr. Bernard Fry at Sheffield. I was
immediately hooked! Here was one of the first scientific conundrums I
faced: are bacteriophage dead or alive? Is a biological "system" that requires the "machinery" of a bacterial host to replicate (phage,
incidentally outnumber most species on the planet), a living organism
or an inert molecule? For me it sparked an interest in the origin of
life, and it
also sparked another interest, in the area molecular structure and
function. Our appetites (well those of us who found these lectures
fascinating) were whetted further by what felt at the time to be
powerful Electron Microscopy (EM) images. Fifty years on from these classic experiments, in the light of the marvellous structural biology images of multi-subunit enzymes such as the ribosome, with which we have become so familiar; the early EMs appear, well, maybe a little dated?
As me and my classmates passed through the various Biochemistry lecture
courses in metabolism and enzymology, we finally caught up with these
strange hybrids between living organisms and molecular assemblies in
crystallography lectures, when Professor Pauline Harrison showed us
images of the plant virus: Tobacco Mosaic Virus (RHS). It was clear that
phage and viruses would hold a beauty that just needed time and patience, and the development of better methods of sample preparation, data collection and analysis, for high resolution structures to emerge. Well those methods have
finally arrived and the technique of cryo EM is now set to provide us
with molecular details of these macromolecular machines. I shall provide a small amount of background information to help provide a context to the work. 
The mechanism of phage infection differs from the viral infection of eukaryotic cells, since the latter are generally free from a peptidoglycan layer.
Phage such as T4 (one of the T-even phages) make an initial interaction
with a surface molecule (part of the peptidoglycan wall), which is followed by the release of the "landing gear", or the tail fibres and base plate. [The nomenclature of phage is a little idiosyncratic, but the
T even phage are collectively more complex in structure than the T odd
phage (T5, T7 etc): the T odd group do not have a contractile sheath,
but rather a tail]. I wont say much more about the T odd phages here.
Eukaryotic viruses generally make similar interactions, but then, owing
to the similarity of the viral "coat" to a plasma membrane, a fusion event takes place. However, I won't say anything further about viruses, either, for now. T4 phage all possess a geometrically symmetrical head or capsid, in which around 170 000 base pairs of genomic DNA are packaged. The focus of this post is the base plate, sheath and landing gear which surround the "syringe" like structure, used by T4 to inject its genomic payload into its chosen host. An incredible piece of nano-architecture! A few words now about the methodology employed, since the experimental methodology underpinning this work is itself a tour de force. First the source material: the authors used a classic phage T4 mutant in order to persuade the host to mass produce the base-plate in the absence of the capsid, drawing on a fine piece of bacterial genetics which provided phage molecular biologists the opportunity to map assembly pathways. Take a look at the lab web site of Jonathan King at MIT: still going strong after some remarkable work in the late '60s and early '70s. Taylor et al used a mutant phage that fails to complete assembly, but instead leads to the accumulation of base plates in the host. From such cells, it is possible to obtain mg quantities of the protein complex, in a homogeneous form; ideal fro the downstream cryo -EM analysis. A superb example of the powerful combination of bacterial genetics and biochemistry.
The development of the electron microscope in
Berlin in the late 1930s (the image RHS was taken in 1940), provided post-war physicists and biologists
with a powerful method for visualising viruses and bacteriophage in
particular. (Not forgetting the pioneering work
at the same time from George Palade and others on the ultra-structure
of mammalian and plant cells). As you can see above, the images reveal a clear attachment of numerous phage particles around the cell wall of the host with mature viruses either inside or laying flat on the surface of the host. However it wasn't until the 1990s that sample preparation combined with image processing methods made it possible to begin to see detail in the images.
It should be noted that X-ray crystallographers (using single crystals) had by the turn of this century, been successful in obtaining high resolution structures of "spherical" virus particles such as Tomato Bushy Stunt Virus. However, the last ten years has seen a gradual shift in technology, amongst structural biologists away from X-ray crystallography towards cryo-EM for the determination of multi-protein assemblies. As with all structure determination methods (including NMR), it will undoubtedly be the case that structural analysis and the interpretation of structure and function will benefit from the judicious choice of technique, depending on the question being asked. You can find a recent summary of cryo-EM technology here at the Baumeister Lab Home Page.So, armed with a nice "production method" for base-plate particle and cryo-EM technology capable of resolving such particles at molecular resolution, Taylor et al have built on the work of Michael Rossmann's Lab and determined the structure of the T4 base plate, providing clues to the attachment and pre-injection stages of phage infection. The three stages:airborne (pre-attachment), approaching the target and landing (attachment) are intuitively clear from the structural models calculated from the electron density aided by published crystal structures of some of the individual components, and shown below (and in more detail here).
As a Biochemist with a leaning towards Biophysics, the question that immediately presents itself to me is: how does folded (compact) conformation change to the extended landing conformation? Any protein synthesised in the cell (or sometimes in the test-tube) folds (almost) spontaneously into its final shape (see an earlier post on protein folding and ebola virus here). Coalescence of hydrophobic side chains and subsequent coating of the protein surface with polar side chains drives the formation of soluble globular proteins. We also know that allosteric enzymes are poised in an equilibrium between two conformational states (active and inactive) and that small ligands can tip the equilibrium over to favour one of the two conformations. It seems to me that the forces that stabilise the folded legs are considerably weaker than those that persuade the legs to extend and clamp onto the surface of the appropriate host cell surface. (Imagine a set of legs that are jointed and ferromagnetic, stabilised in the folded state by the magnetic surface underneath the base-plate, being induced to unfold by a surface that is much more strongly magnetic: the bacterial cell wall).
The final point I want to make relates to the extended structures that form the legs and the injection tube, or spike. I have captured an image from the protein data base of the small T4 protein gp5 (see RHS). If you look closely the spike is a cylinder formed from beta sheets. The spike ends in a tip that penetrates the bacterial cell and injects the DNA. What a fantastic example of structure and function in Nature at the molecular level. Similarly, the legs are extended structures which remind me of the extended helix in the calcium sensor protein calmodulin. Such structures are intrinsically unstable in the sense that they are vulnerable to proteases, however, when I see a crane on a large building site, I think of the engineering design that makes the tall structre sufficiently stable to move around heavy objects. Nature has achieved similar fetes at the molecular level....and this structure has many more features than I have touched on, so please read the article in Nature if you can access it, or go to Petr Leiman's web site here. 
