First X-Ray Diffraction Image of a Single Virus Particle
X-ray crystallography has been an important technique for biologists since the 1940s and 50s, revealing the three-dimensional structure of complex biological molecules such as haemoglobin, DNA and viruses. But the technique has a severe limitation: it only works with molecules that form into crystals and that turns out to be a tiny fraction of the proteins that make up living things. A team of US researchers have created the first image of a single uncrystallized virus particle using x-ray diffraction.
The virus they studied was murine herpesvirus-68 (MHV-68). A herpes virion has an asymmetric tegument and envelope outside of the icosahedrally symmetric capsid composed of defined numbers of subunits. However, each virion may have a different size of tegument and envelope, and the virus capsid is not necessarily in the center of the virion. While cryo-electron microscopy can determine the capsid structure of herpesviruses by averaging over thousands of virus particles, the reconstructions of pleomorphic virions obtained by cryo-electron tomography are limited in low image contrast and high levels of noise.
The trick with the new technique is to take a diffraction pattern of the virus and then subtract the diffraction pattern of its surroundings. This breakthrough paves the way for scientists to start teasing apart the three-dimensional structures of the many viruses and proteins that have eluded biologists to date.
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Quantitative Imaging of Single, Unstained Viruses with Coherent X-rays. 2008 arXiv:0806.2875v1
Since Perutz, Kendrew and colleagues unveiled the structure of hemoglobin and myoglobin based on X-ray diffraction analysis in the 1950s, X-ray crystallography has become the primary methodology used to determine the 3D structure of macromolecules. However, biological specimens such as cells, organelles, viruses and many important macromolecules are difficult or impossible to crystallize, and hence their structures are not accessible by crystallography. Here we report, for the first time, the recording and reconstruction of X-ray diffraction patterns from single, unstained viruses. The structure of the viral capsid inside a virion was visualized. This work opens the door for quantitative X-ray imaging of a broad range of specimens from protein machineries, viruses and organelles to whole cells. Moreover, our experiment is directly transferable to the use of X-ray free electron lasers, and represents a major experimental milestone towards the X-ray imaging of single macromolecules.
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Tags: Biology, Microbiology, Podcast, Science, Video, Virology
