6Z9M

Pseudoatomic model of the pre-fusion conformation of glycoprotein B of Herpes simplex virus 1

Replaces:  5FZ2

Summary for 6Z9M

• Entry DOI: 10.2210/pdb6z9m/pdb
• EMDB information: 11123 3362
• Descriptor: Envelope glycoprotein B (1 entity in total)
• Functional Keywords: membrane fusion protein, glycoprotein, gb, ul27, viral entry protein, class iii fusion protein, transmembrane protein, pre-fusion conformation, viral protein
• Biological source: Human herpesvirus 1 (HHV-1)
• Total number of polymer chains: 3
• Total formula weight: 301149.91

Authors

Vollmer, B.,Prazak, V.,Vasishtan, D.,Jefferys, E.E.,Hernandez-Duran, A.,Vallbracht, M.,Klupp, B.,Mettenleiter, T.C.,Backovic, M.,Rey, F.A.,Topf, M.,Gruenewald, K. (deposition date: 2020-06-04, release date: 2020-10-07, Last modification date: 2024-11-13)

Primary citation

Vollmer, B.,Prazak, V.,Vasishtan, D.,Jefferys, E.E.,Hernandez-Duran, A.,Vallbracht, M.,Klupp, B.G.,Mettenleiter, T.C.,Backovic, M.,Rey, F.A.,Topf, M.,Grunewald, K.
The prefusion structure of herpes simplex virus glycoprotein B.
Sci Adv, 6:-, 2020

PubMed 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.

PubMed: 32978151
DOI: 10.1126/sciadv.abc1726

Experimental method

ELECTRON MICROSCOPY (9.1 Å)