The polyhedral heads of viruses that infect bacteria may look like the capsules of lunar landers, but at least one of them knows a trick that is purely medieval. The head or "capsid" of that bacteriophage, described for the first time in the 22 September issue of Science, wraps itself in rings of proteins that ingeniously interlock like links of chain-mail armor.
Scientists have long been taking electron micrographs of phages injecting bacteria with DNA from their polygon-tiled holds. But more detailed images have been slow in coming, largely because the technique that produces them--x-ray crystallography--requires a technically challenging preparation of viral parts. As a result, none of the so-called tailed phages--the archetypal bacterial viruses--has yielded a detailed capsid structure.
Virologists at the University of Pittsburgh harvested capsids of the so-called lambda-like phage HK97 from bacteria they had infected with two viral genes: one encoding the protein that serves as the capsid's sole building block, and the other encoding an enzyme that cuts the protein so that capsids can mature. Next, structural biologists at the Scripps Research Institute and at Stanford University used synchrotrons to create x-ray diffraction patterns from the capsids. Thanks to microscope images and their knowledge of the capsid's symmetry, the researchers could then piece together a detailed picture of the virus.
They discovered the capsid consists of 420 identically folded protein subunits grouped into 60 hexagonal and 12 pentagonal tiles. Through chemical bonds, the subunits form 5- and 6-membered necklaces, which weave through one another like the Olympic rings. To understand how the subunits knit themselves together, the team displayed microscope images of knobby, immature capsids on a computer screen and then superimposed pictures of the 420 subunits. They knew that the trigger for the interweaving process is a change in pH. When the virus's environment turns more acidic, the capsid smoothes and swells by about a third of its diameter. As that happens, the subunits on its surface swivel in a way that brings together the asparagine and lysine side chains that link neighboring subunits. A nearby glutamate side chain appears to catalyze the unlikely linkage, which occurs without aid of enzymes. Like real chain mail, the researchers say, the interlaced proteins armor hk97 against onslaughts that might otherwise dislodge the virus's DNA innards.
No one has ever seen rings of linking proteins before, says biophysicist Peter Prevelige of the University of Alabama at Birmingham. Nor, he adds, could he have imagined a protein pulling all of the stunts that the HK97 subunit does. Says Prevelige: "If anybody had suggested it, I'd have thought the idea came from too many beers."