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An assembly model of rift valley Fever virus.

Rusu M, Bonneau R, Holbrook MR, Watowich SJ, Birmanns S, Wriggers W, Freiberg AN - Front Microbiol (2012)

Bottom Line: Furthermore, Gc is suggested to facilitate intercapsomer connections.The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins.Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Informatics, University of Texas Health Science Center at Houston Houston, TX, USA.

ABSTRACT
Rift Valley fever virus (RVFV) is a bunyavirus endemic to Africa and the Arabian Peninsula that infects humans and livestock. The virus encodes two glycoproteins, Gn and Gc, which represent the major structural antigens and are responsible for host cell receptor binding and fusion. Both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. Currently, no experimental three-dimensional structure for any entire bunyavirus glycoprotein is available. Using fold recognition, we generated molecular models for both RVFV glycoproteins and found significant structural matches between the RVFV Gn protein and the influenza virus hemagglutinin protein and a separate match between RVFV Gc protein and Sindbis virus envelope protein E1. Using these models, the potential interaction and arrangement of both glycoproteins in the RVFV particle was analyzed, by modeling their placement within the cryo-electron microscopy density map of RVFV. We identified four possible arrangements of the glycoproteins in the virion envelope. Each assembly model proposes that the ectodomain of Gn forms the majority of the protruding capsomer and that Gc is involved in formation of the capsomer base. Furthermore, Gc is suggested to facilitate intercapsomer connections. The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins. Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.

No MeSH data available.


Related in: MedlinePlus

Capsomer twofold axis; (A,C) first; (B,D) second; (E,G) third; (F,H) fourth top-scoring model.
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FA1: Capsomer twofold axis; (A,C) first; (B,D) second; (E,G) third; (F,H) fourth top-scoring model.

Mentions: We applied the described procedure (Figure 2) to 11xGn/Gc pairs obtained by combining the interactively selected Gc and Gn glycoproteins. Some of these pairs were discarded during the modeling as it become apparent that they prevented the generation of models with good stereochemical quality and appropriate Gn/Gc ratios. At the end of the procedure, four models were produced with cross-correlation coefficients above 0.783 (Figures A1–A4 in Appendix). The top scoring model had a correlation of 0.798 and is shown in Figures 3 and 4. This model had an estimated volume of approx. 1,300,000 Å3 for the hexon and approximately 1,100,000 Å3 for the pentons, in agreement with our previous calculations (Sherman et al., 2009).


An assembly model of rift valley Fever virus.

Rusu M, Bonneau R, Holbrook MR, Watowich SJ, Birmanns S, Wriggers W, Freiberg AN - Front Microbiol (2012)

Capsomer twofold axis; (A,C) first; (B,D) second; (E,G) third; (F,H) fourth top-scoring model.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3400131&req=5

FA1: Capsomer twofold axis; (A,C) first; (B,D) second; (E,G) third; (F,H) fourth top-scoring model.
Mentions: We applied the described procedure (Figure 2) to 11xGn/Gc pairs obtained by combining the interactively selected Gc and Gn glycoproteins. Some of these pairs were discarded during the modeling as it become apparent that they prevented the generation of models with good stereochemical quality and appropriate Gn/Gc ratios. At the end of the procedure, four models were produced with cross-correlation coefficients above 0.783 (Figures A1–A4 in Appendix). The top scoring model had a correlation of 0.798 and is shown in Figures 3 and 4. This model had an estimated volume of approx. 1,300,000 Å3 for the hexon and approximately 1,100,000 Å3 for the pentons, in agreement with our previous calculations (Sherman et al., 2009).

Bottom Line: Furthermore, Gc is suggested to facilitate intercapsomer connections.The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins.Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Informatics, University of Texas Health Science Center at Houston Houston, TX, USA.

ABSTRACT
Rift Valley fever virus (RVFV) is a bunyavirus endemic to Africa and the Arabian Peninsula that infects humans and livestock. The virus encodes two glycoproteins, Gn and Gc, which represent the major structural antigens and are responsible for host cell receptor binding and fusion. Both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. Currently, no experimental three-dimensional structure for any entire bunyavirus glycoprotein is available. Using fold recognition, we generated molecular models for both RVFV glycoproteins and found significant structural matches between the RVFV Gn protein and the influenza virus hemagglutinin protein and a separate match between RVFV Gc protein and Sindbis virus envelope protein E1. Using these models, the potential interaction and arrangement of both glycoproteins in the RVFV particle was analyzed, by modeling their placement within the cryo-electron microscopy density map of RVFV. We identified four possible arrangements of the glycoproteins in the virion envelope. Each assembly model proposes that the ectodomain of Gn forms the majority of the protruding capsomer and that Gc is involved in formation of the capsomer base. Furthermore, Gc is suggested to facilitate intercapsomer connections. The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins. Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.

No MeSH data available.


Related in: MedlinePlus