SARS CoV-2 spike adopts distinct conformational ensembles in situ DOI Open Access

Amanda J. Gramm,

Sean M. Braet, Bindu Y. Srinivasu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

ABSTRACT Engineered recombinant Spike (S) has been invaluable for determining S structure and dynamics is the basis design of most prevalent vaccines. While these vaccines have highly efficacious short-term protection from infection, waned with emergence variants (alpha through omicron). Here we report differences in conformational between native, membrane-embedded full-length S. Our virus-like particle (VLP) model mimics native SARS CoV-2 virion by displaying assembled auxiliary E, M, N proteins a membrane environment that captures entirety quaternary interactions mediated Display on VLP obviates requirement stabilizing modifications engineered into enhanced expression solubility. Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) reveals altered interprotomer contacts trimers attributable to presence proteins, anchoring, lack modifications. results reveal decreased S2 subunit at sites spanning minimal N-terminal domain (NTD) receptor binding (RBD). This carries implications display epitopes beyond NTD RBD. In summary, despite affording efficient structural characterization, distorts intrinsic ensemble displayed virus surface.

Language: Английский

A coronavirus assembly inhibitor that targets the viral membrane protein DOI Creative Commons
Manon Laporte, Dirk Jochmans,

Dorothée Bardiot

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

3
SARS CoV-2 spike adopts distinct conformational ensembles in situ DOI Open Access

Amanda J. Gramm,

Sean M. Braet, Bindu Y. Srinivasu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

ABSTRACT Engineered recombinant Spike (S) has been invaluable for determining S structure and dynamics is the basis design of most prevalent vaccines. While these vaccines have highly efficacious short-term protection from infection, waned with emergence variants (alpha through omicron). Here we report differences in conformational between native, membrane-embedded full-length S. Our virus-like particle (VLP) model mimics native SARS CoV-2 virion by displaying assembled auxiliary E, M, N proteins a membrane environment that captures entirety quaternary interactions mediated Display on VLP obviates requirement stabilizing modifications engineered into enhanced expression solubility. Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) reveals altered interprotomer contacts trimers attributable to presence proteins, anchoring, lack modifications. results reveal decreased S2 subunit at sites spanning minimal N-terminal domain (NTD) receptor binding (RBD). This carries implications display epitopes beyond NTD RBD. In summary, despite affording efficient structural characterization, distorts intrinsic ensemble displayed virus surface.

Language: Английский

Citations

0