Vollmer, B;
Pražák, V;
Vasishtan, D;
Jefferys, EE;
Hernandez-Duran, A;
Vallbracht, M;
Klupp, BG;
... Grünewald, K; + view all
(2020)
The prefusion structure of herpes simplex virus glycoprotein B.
Science Advances
, 6
(39)
, Article eabc1726. 10.1126/sciadv.abc1726.
Preview |
Text
eabc1726.full.pdf - Published Version Download (9MB) | Preview |
Abstract
Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins.
| Type: | Article |
|---|---|
| Title: | The prefusion structure of herpes simplex virus glycoprotein B. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.abc1726 |
| Publisher version: | https://doi.org/10.1126/sciadv.abc1726 |
| Language: | English |
| Additional information: | Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10115552 |
Archive Staff Only
 |
View Item |
