6wko

From Proteopedia

Structure of an influenza C virus hemagglutinin-esterase-fusion (HEF2) intermediate

Structural highlights

6wko is a 1 chain structure with sequence from Influenza C virus (C/Johannesburg/1/66). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.401Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HEMA_INCJH Binds to the N-acetyl-9-O-acetylneuraminic acid residues on the cell surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induce an irreversible conformational change in HEF2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Displays a receptor-destroying activity which is a neuraminidate-O-acetyl esterase. This activity cleaves off any receptor on the cell surface, which would otherwise prevent virions release. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell.

Publication Abstract from PubMed

Enveloped virus entry requires the fusion of cellular and viral membranes, a process directed by their viral fusion glycoproteins. Our current knowledge of this process has been shaped by structural studies of the pre- and post-fusion conformations of these viral fusogens. These structural snapshots have revealed the start and end states necessary for fusion, but the dynamics of the intermediate conformations have remained unclear. Using the influenza C virus hemagglutinin-esterase-fusion glycoprotein as a model, we report the structural and biophysical characterization of a trapped intermediate. Crystallographic studies revealed a structural reorganization of the C terminus to create a second chain reversal region, resulting in the N and C termini being positioned in opposing directions. Intrinsic tryptophan fluorescence and bimane-induced quenching measurements suggest intermediate formation is mediated by conserved hydrophobic residues. Our study reveals a late-stage extended intermediate structural event. This work adds to our understanding of virus cell fusion.

Snapshot of an influenza virus glycoprotein fusion intermediate.,Serrao VHB, Cook JD, Lee JE Cell Rep. 2021 May 18;35(7):109152. doi: 10.1016/j.celrep.2021.109152. PMID:34010634^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Serrao VHB, Cook JD, Lee JE. Snapshot of an influenza virus glycoprotein fusion intermediate. Cell Rep. 2021 May 18;35(7):109152. doi: 10.1016/j.celrep.2021.109152. PMID:34010634 doi:http://dx.doi.org/10.1016/j.celrep.2021.109152