Unveiling the Complete Spectrum of SARS-CoV-2 Fusion Stages by In Situ Cryo-ET DOI Creative Commons
Caner Akıl,

Jialu Xu,

Juan Shen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM has revealed stable prefusion and postfusion conformations of spike, transient intermediate states during fusion process have remained poorly understood. Here, we designed a near-native viral system that recapitulates SARS- CoV-2 used cryo-electron tomography (cryo-ET) to capture intermediates leading complete The protein undergoes extensive structural rearrangements, progressing through extended, partially folded, fully folded prior fusion-pore formation, dependent on protease cleavage inhibited WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at interfaces following S2' concurrently transition encircling hemifusion pre-fusion pores in distinct conical arrangement. Subtomogram averaging antibody binds spike's stem-helix, crosslinks clusters inhibits refolding intermediates. These findings elucidate spike-mediated entry, highlighting neutralizing mechanism S2-targeting antibodies.

Язык: Английский

Unveiling the Complete Spectrum of SARS-CoV-2 Fusion Stages by In Situ Cryo-ET DOI Creative Commons
Caner Akıl,

Jialu Xu,

Juan Shen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM has revealed stable prefusion and postfusion conformations of spike, transient intermediate states during fusion process have remained poorly understood. Here, we designed a near-native viral system that recapitulates SARS- CoV-2 used cryo-electron tomography (cryo-ET) to capture intermediates leading complete The protein undergoes extensive structural rearrangements, progressing through extended, partially folded, fully folded prior fusion-pore formation, dependent on protease cleavage inhibited WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at interfaces following S2' concurrently transition encircling hemifusion pre-fusion pores in distinct conical arrangement. Subtomogram averaging antibody binds spike's stem-helix, crosslinks clusters inhibits refolding intermediates. These findings elucidate spike-mediated entry, highlighting neutralizing mechanism S2-targeting antibodies.

Язык: Английский

Процитировано

0