Bilayer-bound structure of SARS-CoV-2 Envelope protein in complex with a host PDZ domain
- 1Max Planck Institute for Multidisciplinary Sciences
Abstract
Small multifunctional viral membrane proteins called viroporins are attractive drug targets but are difficult to structurally characterize in a lipid-bilayer environment. We have successfully reconstituted the full-length Envelope (E) protein from SARS-CoV-2 in a lipid-bilayer, co-assembled with a native host factor that binds to E, the PDZ domain 2 of ZO1. We have leveraged the enhancement afforded by dynamic nuclear polarization NMR to determine that the ensemble-averaged oligomer state of E is a pentamer. Complexing the protein with a host PDZ domain did not impact the oligomer state, but resulted in structuring of the last four residues of E, and immobilization of the PDZ domain near the lipid surface. Combined with secondary structure information derived from the chemical shifts, these data were used to model an E protein pentamer together with the PDZ protein dimer. Inclusion of a relevant host factor, as well as a complex lipid bilayer that mimics conditions in the ER-Golgi intermediate compartment, approaches native conditions, and addresses the ongoing controversy regarding the functional oligomer state in an infected cell.
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BibTeX
@misc{varkey2026bilayerbound,
title = {{Bilayer-bound structure of SARS-CoV-2 Envelope protein in complex with a host PDZ domain}},
author = {A. C. Varkey and E. Nimerovsky and K. Xue and C. Schwiegk and K. Giller and S. Becker and L. B. Andreas},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.756756},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.756756v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Bilayer-bound structure of SARS-CoV-2 Envelope protein in complex with a host PDZ domain
AU - A. C. Varkey
AU - E. Nimerovsky
AU - K. Xue
AU - C. Schwiegk
AU - K. Giller
AU - S. Becker
AU - L. B. Andreas
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.756756
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.756756v1
AB - Small multifunctional viral membrane proteins called viroporins are attractive drug targets but are difficult to structurally characterize in a lipid-bilayer environment. We have successfully reconstituted the full-length Envelope (E) protein from SARS-CoV-2 in a lipid-bilayer, co-assembled with a native host factor that binds to E, the PDZ domain 2 of ZO1. We have leveraged the enhancement afforded by dynamic nuclear polarization NMR to determine that the ensemble-averaged oligomer state of E is a pentamer. Complexing the protein with a host PDZ domain did not impact the oligomer state, but resulted in structuring of the last four residues of E, and immobilization of the PDZ domain near the lipid surface. Combined with secondary structure information derived from the chemical shifts, these data were used to model an E protein pentamer together with the PDZ protein dimer. Inclusion of a relevant host factor, as well as a complex lipid bilayer that mimics conditions in the ER-Golgi intermediate compartment, approaches native conditions, and addresses the ongoing controversy regarding the functional oligomer state in an infected cell.
ER -