|Publication type:||Article in scientific journal|
|Type of review:||Peer review (publication)|
|Title:||Structure and supramolecular organization of the canine distemper virus attachment glycoprotein|
|Published in:||Proceedings of the National Academy of Sciences of the United States of America|
|Publisher / Ed. Institution:||National Academy of Sciences|
|Subjects:||H-protein ectodomain; Canine distemper virus; Cryo-electron microscopy; Morbillivirus cell entry; Structure|
|Subject (DDC):||579: Microbiology|
|Abstract:||Canine distemper virus (CDV) is an enveloped RNA morbillivirus that triggers respiratory, enteric, and high incidence of severe neurological disorders. CDV induces devastating outbreaks in wild and endangered animals as well as in domestic dogs in countries associated with suboptimal vaccination programs. The receptor-binding tetrameric attachment (H)-protein is part of the morbilliviral cell entry machinery. Here, we present the cryo-electron microscopy (cryo-EM) structure and supramolecular organization of the tetrameric CDV H-protein ectodomain. The structure reveals that the morbilliviral H-protein is composed of three main domains: stalk, neck, and heads. The most unexpected feature was the inherent asymmetric architecture of the CDV H-tetramer being shaped by the neck, which folds into an almost 90° bent conformation with respect to the stalk. Consequently, two non-contacting receptor-binding H-head dimers, which are also tilted toward each other, are located on one side of an intertwined four helical bundle stalk domain. Positioning of the four protomer polypeptide chains within the neck domain is guided by a glycine residue (G158), which forms a hinge point exclusively in two protomer polypeptide chains. Molecular dynamics simulations validated the stability of the asymmetric structure under near physiological conditions and molecular docking showed that two receptor-binding sites are fully accessible. Thus, this spatial organization of the CDV H-tetramer would allow for concomitant protein interactions with the stalk and head domains without steric clashes. In summary, the structure of the CDV H-protein ectodomain provides new insights into the morbilliviral cell entry system and offers a blueprint for next-generation structure-based antiviral drug discovery.|
|Fulltext version:||Published version|
|License (according to publishing contract):||Licence according to publishing contract|
|Departement:||Life Sciences and Facility Management|
|Organisational Unit:||Institute of Chemistry and Biotechnology (ICBT)|
|Appears in collections:||Publikationen Life Sciences und Facility Management|
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Kalbermatter, D., Jeckelmann, J.-M., Wyss, M., Shrestha, N., Pliatsika, D., Riedl, R., Lemmin, T., Plattet, P., & Fotiadis, D. (2023). Structure and supramolecular organization of the canine distemper virus attachment glycoprotein. Proceedings of the National Academy of Sciences of the United States of America, 120(6), e2208866120. https://doi.org/10.1073/pnas.2208866120
Kalbermatter, D. et al. (2023) ‘Structure and supramolecular organization of the canine distemper virus attachment glycoprotein’, Proceedings of the National Academy of Sciences of the United States of America, 120(6), p. e2208866120. Available at: https://doi.org/10.1073/pnas.2208866120.
D. Kalbermatter et al., “Structure and supramolecular organization of the canine distemper virus attachment glycoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 6, p. e2208866120, Feb. 2023, doi: 10.1073/pnas.2208866120.
Kalbermatter, David, et al. “Structure and Supramolecular Organization of the Canine Distemper Virus Attachment Glycoprotein.” Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 6, Feb. 2023, p. e2208866120, https://doi.org/10.1073/pnas.2208866120.
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