7QRG

Structure of the post-fusion complex between precursor membrane ectodomain (prM) and envelope ectodomain protein (E) from tick-borne encephalitis virus

Summary for 7QRG

• Entry DOI: 10.2210/pdb7qrg/pdb
• Related: 7QRE 7QRF
• Descriptor: Envelope protein E, Genome polyprotein, GLYCEROL, ... (4 entities in total)
• Functional Keywords: class ii fusion envelope protein, precursor membrane protein, chaperone, post-fusion, flavivirus, viral protein
• Biological source: Tick-borne encephalitis virus (WESTERN SUBTYPE); More
• Total number of polymer chains: 2
• Total formula weight: 63271.86

Authors

Vaney, M.C.,Rouvinski, A.,Rey, F.A. (deposition date: 2022-01-11, release date: 2022-05-25, Last modification date: 2024-10-23)

Primary citation

Vaney, M.C.,Dellarole, M.,Duquerroy, S.,Medits, I.,Tsouchnikas, G.,Rouvinski, A.,England, P.,Stiasny, K.,Heinz, F.X.,Rey, F.A.
Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery.
Nat Commun, 13:3718-3718, 2022

PubMed Abstract: The flavivirus envelope glycoproteins prM and E drive the assembly of icosahedral, spiky immature particles that bud across the membrane of the endoplasmic reticulum. Maturation into infectious virions in the trans-Golgi network involves an acid-pH-driven rearrangement into smooth particles made of (prM/E) dimers exposing a furin site for prM cleavage into "pr" and "M". Here we show that the prM "pr" moiety derives from an HSP40 cellular chaperonin. Furthermore, the X-ray structure of the tick-borne encephalitis virus (pr/E) dimer at acidic pH reveals the E 150-loop as a hinged-lid that opens at low pH to expose a positively-charged pr-binding pocket at the E dimer interface, inducing (prM/E) dimer formation to generate smooth particles in the Golgi. Furin cleavage is followed by lid-closure upon deprotonation in the neutral-pH extracellular environment, expelling pr while the 150-loop takes the relay in fusion loop protection, thus revealing the elusive flavivirus mechanism of fusion activation.

PubMed: 35764616
DOI: 10.1038/s41467-022-31111-y

Experimental method

X-RAY DIFFRACTION (2.8 Å)