NSRRC Activity Report 2023

050 NSRRC ACTIVITY REPORT 2023 On the other hand, Hsu’s team constructed a single chain incorporating the HR1 and HR2 peptide segments connected through an L6 linker (referred to as HR1–L6–HR2) and conducted a series of experiments to investigate its structure and stability. They observed the spontaneous assembly of this protein into a highly stable trimeric complex. Crystallographic analysis revealed a trimeric coiled-coil structure in the fusion core ( Fig. 3(a) ), 1 with specific residues involved in binding. The research team suggested that the fusion core of SARS-CoV-2 shares a similar conformation with those of other class I viruses, remarkably resembling the fusion core of SARS-CoV spike protein ( Fig. 3(b) ). 1 This indicates the possibility of employing similar methods to identify inhibitors effective against SARS-CoV-2 infection. Additionally, this structure provides crucial detailed information and target sites for structure-based drug design. In summary, both studies elucidated the structural characteristics and biophysical properties of the RBD and fusion core. They noted that these features are essential in developing vaccines and therapeutic approaches for SARS-CoV-2 and other sarbecoviruses within the Coronaviridae family. (Reported by Chun-Hsiang Huang) This report features the work of Che Ma, Chun-Hua Hsu and their co-workers published in Nat. Commun. 14 , 311 (2023) and J. Chin. Chem. Soc. 70 , 1208 (2023). TPS 05A Protein Microcrystallography TLS 15A1 Biopharmaceuticals Protein Crystallography • XPS, Protein Crystallography • Biological Macromolecules, Protein Structures, Life Science References 1. C.-H Hsu, J. Chin. Chem. Soc. 70 , 1208 (2023). 2. K.-Y. A. Huang, X. Chen, A. Mohapatra, H. T. V. Nguyen, L. Schimanski, T. K. Tan, P. Rijal, S. K. Vester, R. A. Hills, M. Howarth, J. R. Keeffe, A. A. Cohen, L. M. Kakutani, Y.-M. Wu, M. Shahed-Al-Mahmud, Y.-C. Chou, P. J. Bjorkman, A. R. Townsend, C. Ma, Nat. Comum. 14 , 311 (2023). T aiwan’s warm temperatures, humid climate, and diverse array of nectar sources create a favorable environment for fostering honeybee habitats and promoting their propagation. Honeybees, in turn, play a crucial role in pollinating wild plants and agricultural crops. The two major honeybees, Apis cerana Fabricius ( A. cerana ) (Eastern honeybee) and Apis mellifera Linnaeus ( A. mellifera ) (Western honeybee) both play a crucial role in contributing to commercially valuable honey harvests and are both major honeybee species in the global beekeeping industry. 1 Colony collapse disorder (CCD) is a noteworthy phenomenon characterized by the sudden disappearance of as much as 90% of beehives in apiaries. Pathogens, including viruses, bacteria, fungi, mites, and environmental factors, such as chemical exposure and forage availability, have been identified as major contributors to disease in managed honeybee populations and are often associated with CCD. 2 Although the precise mechanisms of CCD remain elusive, evidence suggests that a newly discovered Secrets of the Deadly Honeybee-Infecting Virus Unveiled The atomic-resolution capsid structure of the honeybee-infecting virus could furnish valuable insights into the mechanisms governing viral capsid assembly, function, and infection with dynamic motions. This information can be harnessed for the development of natural drugs for honeybee colony protection. honeybee-infecting virus, Lake Sinai virus (LSV), plays a key role in this devastating disorder. The primary strains of LSV encompass two principal types, namely LSV1 and LSV2, along with other variants. LSV comprises a characteristic T = 4 quasi-equivalence nonenveloped capsid for packaging the single-stranded positive-sense RNA genome. The RNA genome size is ~5.6 kb and it encodes three major genes: Orf1 with unknown function, RNA-dependent RNA polymerase responsible for viral RNA replication, and the capsid protein (CP) for host recognition and viral capsid assembly. This work aims to explore the structures of LSV virus-like particles (VLPs), characterize all domain functions, and understand capsid assembly and RNA packaging during viral infection. Although mature LSV virions are generally considered to exist solely in T = 4 assemblies, cryo-electron microscopy (cryo-EM) analyses of LSV2 and delta-N48 LSV1 VLPs uncovered structural polymorphism. By examining