Diamond Annual Review 2023/24

18 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 3 / 2 4 A historical virus sample reveals a novel protein structure Two families of insect viruses - the double-stranded DNA Baculoviridae and double-stranded RNA cypoviruses - are known for using protein crystals, called polyhedra, to encase virus particles. The notable feature of the polyhedra is their remarkable resilience, protecting the viruses inside from environmental factors such as temperature, light, and water. Recent research has found that at least one genus of nudiviruses form polyhedra that were not previously recognised.​ Researchers analysed frozen samples originally purified in the '1960's' to investigate the structure of nudivirus polyhedra. Using X-ray crystallography on the VMXm beamline, the research team solved the lattice structure of a polyhedrin (occlusion body) from Nudiviridae, which adds to our knowledge of how viruses use protein self-assembly to protect themselves from the environment.​ The 70-year-old sample contains a well-ordered lattice formed by a predominantly α-helical building block that assembles into a dense, highly interconnected protein crystal. The lattice is maintained by extensive hydrophobic and electrostatic interactions, disulfide bonds, and domain switching. The resulting lattice is resistant to most environmental stresses. Comparison of this structure to baculovirus or cypovirus polyhedra shows a distinct protein structure, crystal space group, and unit cell dimensions. Keown, J.R. et al. DOI: 10.1038/ s41467-023-39819-1​ Fighting back against devastating parasites Chagas disease and leishmaniasis are two examples of Neglected Tropical Diseases (NTDs), a diverse group of 20 conditions that cause devastating health, social and economic consequences for over one billion people worldwide. These diseases often afflict the poorest and most marginalised communities, leading to significant health and economic burdens and disproportionately affecting women and children. ​ However, historically they have not received asmuch attention and funding for research and control efforts as other major infectious diseases. ​ Trypanosoma cruzi , which causes Chagas disease, and the 20+ species of Leishmania that cause leishmaniasis are trypanosomatid organisms. Another trypanosomatid, Trypanosoma theileri , infects livestock such as sheep and cattle. All of these parasites have a complex life cycle, involving both an insect vector and a mammalian host. They require trypanothione to survive in their host organisms, which they produce via cysteine biosynthesis. By using the I24 beamline, researchers obtained high-resolution structures of cysteine synthase enzymes from different pathogens.​ Their results allow a greater understanding of cysteine synthase in these organisms and give a starting point for the structure-based design of new drugs to treat these diseases. The team also has plans to test the first new compounds in the lab next year in Chagas Disease mouse models. Research like this is key to the World Health Organisation achieving its goal to prevent, control, eliminate and eradicate neglected tropical diseases by 2030.​ Sowerby, K. et al. DOI: 10.1107/S2059798323003613​ MX Science Highlights Figure: Ribbon diagram of the structure of T. cruzi cysteine synthase in a similar orientation to LiCS and TthCS. Chain A is coloured dark green and chain B is coloured light green. PLP is shown in stick representation. Figure: a) Scanning electron micrograph of native ToNV occlusion bodies prepared for diffraction experiments. Images have been cropped but are otherwise unedited. b) A single polyhedrin molecule coloured from the N-terminus (blue) to the C-terminus (red) and annotated with secondary structure features. A calcium ion is shown (green). The dashed line shows the missing loop 171–174. c) The dimeric unit (red and blue chains) of the OB lattice are shown in two orientations.