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A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.

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Title: A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.
Authors: Guardado-Calvo, P., Atkovska, K., Jeffers, S. A., Grau, N., Backovic, M., Pérez-Vargas, J., de Boer, S. M., Tortorici, M. A., Pehau-Arnaudet, G., Lepault, J., England, P., Rottier, P. J., Bosch, B. J., Hub, J. S., Rey, F. A.
Source: Science (pre-March 2025). 11/3/2017, Vol. 358 Issue 6363, p663-667. 5p. 4 Diagrams.
Subjects: Rift Valley fever, Chimeric proteins, Glycerophospholipids, Molecular dynamics, Mutagenesis
Abstract: The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.
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  Data: <searchLink fieldCode="AR" term="%22Guardado-Calvo%2C+P%2E%22">Guardado-Calvo, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Atkovska%2C+K%2E%22">Atkovska, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Jeffers%2C+S%2E+A%2E%22">Jeffers, S. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Grau%2C+N%2E%22">Grau, N.</searchLink><br /><searchLink fieldCode="AR" term="%22Backovic%2C+M%2E%22">Backovic, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Pérez-Vargas%2C+J%2E%22">Pérez-Vargas, J.</searchLink><br /><searchLink fieldCode="AR" term="%22de+Boer%2C+S%2E+M%2E%22">de Boer, S. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Tortorici%2C+M%2E+A%2E%22">Tortorici, M. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Pehau-Arnaudet%2C+G%2E%22">Pehau-Arnaudet, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Lepault%2C+J%2E%22">Lepault, J.</searchLink><br /><searchLink fieldCode="AR" term="%22England%2C+P%2E%22">England, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Rottier%2C+P%2E+J%2E%22">Rottier, P. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Bosch%2C+B%2E+J%2E%22">Bosch, B. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hub%2C+J%2E+S%2E%22">Hub, J. S.</searchLink><br /><searchLink fieldCode="AR" term="%22Rey%2C+F%2E+A%2E%22">Rey, F. A.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 11/3/2017, Vol. 358 Issue 6363, p663-667. 5p. 4 Diagrams.
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  Data: <searchLink fieldCode="DE" term="%22Rift+Valley+fever%22">Rift Valley fever</searchLink><br /><searchLink fieldCode="DE" term="%22Chimeric+proteins%22">Chimeric proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Glycerophospholipids%22">Glycerophospholipids</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+dynamics%22">Molecular dynamics</searchLink><br /><searchLink fieldCode="DE" term="%22Mutagenesis%22">Mutagenesis</searchLink>
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  Data: The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=126072644
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        Text: English
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        Type: general
      – SubjectFull: Chimeric proteins
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      – SubjectFull: Glycerophospholipids
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      – SubjectFull: Molecular dynamics
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      – SubjectFull: Mutagenesis
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              Text: 11/3/2017
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