Structural biology techniques used to benefit bees and beyond


Just like other animals, bees can contract viruses from parasites like mites. A virus of particular significance is the Deformed Wing Virus (DWV) which has been causing epidemics in western honey bee populations. As the name suggests, DWV causes pupae to be born with deformed wings, but it can also lead to other defects including a shortened abdomen, and cuticle discoloration of adult bees. Bees that survive often die soon after pupation, causing the colony to collapse. In 2017, Dr Nováček helped analyse data to create a detailed 3D picture of the structure of virus.

 

To produce a treatment for the Deformed Wing Virus scientists first need to identify a target. This is where cryo-electron microscopy, and Dr Nováček, come in. By producing a model of the virus on an atomic scale, cryo-EM can be used to identify the best molecular structures to target. The team of researchers have not only ruled out some parts of the structure based on the chemical properties, but they have also identified a potential target for treatment – the ‘P domain’. This domain is needed for the virus to enter a host cell, therefore, is a suitable target for an antiviral treatment. 


Image A shows the P domain, which is part of VP3, is highlighted in magenta. Image B and C show the molecular surfaces of DWV virions determined by cryo-EM (B) and X-ray crystallography (C). (Source: Škubník K, et al. (2017) Structure of deformed wing virus, a major honey bee pathogen. Proc Natl Acad Sci USA 114:3210–3215 https://doi.org/10.1073/pnas.1615695114)



Interpreting information about the structure of biological molecules often requires lots of time from experts. As well as cryo-EM, scientists also use Nuclear Magnetic Resonance (NMR) to determine the location of atoms in a molecule and generate a model. It works well for smaller molecules but there is a problem; larger molecules (like proteins) require up to 10 different readings to be analysed by an expert. 

 

Researchers at the Central European Institute of Technology, including Dr Nováček, have published an algorithm called “4D-CHAINS” to address the challenges of interpreting NMR for proteins. In their paper they conclude that their technique “has a minimal impact on the precision and quality of the resulting structural ensembles, while allowing for a tremendous reduction in human effort and NMR spectrometer time”. By focusing on the application and development of techniques Dr Nováček has had a hand in many scientific developments with potential benefits in a multitude of disciplines. 

 

Read the full Deformed Wing Virus paper: Karel Škubník K., et al., 2017, Structure of deformed wing virus, a major honey bee pathogen, Proceedings of the National Academy of Sciences, 114 (12) 3210-3215

 

Read the fullNMR algorithm paper: Evangelidis, T., et al., 2018, Automated NMR resonance assignments and structure determination using a minimal set of 4D spectra, Nature Communications, 9 (384)

 

To read about NMR facilities at Instrict-ERIC.