A triggering structure of SARS-CoV-2 BA.2.86 spike upon ACE2 binding for receptor-binding domain up
Abstract Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, is believed to bind to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the “up” conformation. However, whether ACE2 exclusively binds to the “up” RBD or also interacts with the “down” RBD to facilitate the conformational shift to RBD-up remains unclear. Here, we present the structures of the BA.2.86 spike alone and bound to ACE2. The N354-linked glycan contributes to the neutralizing antibody evasion in BA.2.86. Notably, we successfully observed the ACE2-bound “down” RBD, indicating a trigger structure before the RBD-up conformation. The wider and mobile angle of RBDs in the “up” state provides space for ACE2 to interact with the “down” RBD, facilitating the transition to the RBD-up state. These structural insights into the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 22. März Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hashiguchi, Takao [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.21203/rs.3.rs-4106877/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA043012752 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA043012752 | ||
| 003 | DE-627 | ||
| 005 | 20240323152855.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240323s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-4106877/v1 |2 doi | |
| 035 | |a (DE-627)XRA043012752 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-4106877/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hashiguchi, Takao |e verfasserin |0 (orcid)0000-0001-7578-7571 |4 aut | |
| 245 | 1 | 0 | |a A triggering structure of SARS-CoV-2 BA.2.86 spike upon ACE2 binding for receptor-binding domain up |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, is believed to bind to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the “up” conformation. However, whether ACE2 exclusively binds to the “up” RBD or also interacts with the “down” RBD to facilitate the conformational shift to RBD-up remains unclear. Here, we present the structures of the BA.2.86 spike alone and bound to ACE2. The N354-linked glycan contributes to the neutralizing antibody evasion in BA.2.86. Notably, we successfully observed the ACE2-bound “down” RBD, indicating a trigger structure before the RBD-up conformation. The wider and mobile angle of RBDs in the “up” state provides space for ACE2 to interact with the “down” RBD, facilitating the transition to the RBD-up state. These structural insights into the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Yajima, Hisano |0 (orcid)0009-0000-0065-4125 |4 aut | |
| 700 | 1 | |a Anraku, Yuki |0 (orcid)0000-0002-5731-0902 |4 aut | |
| 700 | 1 | |a Kaku, Yu |4 aut | |
| 700 | 1 | |a Kimura, Kanako |4 aut | |
| 700 | 1 | |a Plianchaisuk, Arnon |4 aut | |
| 700 | 1 | |a Okumura, Kaho |4 aut | |
| 700 | 1 | |a Nakada-Nakura, Yoshiko |4 aut | |
| 700 | 1 | |a Kita, Shunsuke |0 (orcid)0000-0003-3969-302X |4 aut | |
| 700 | 1 | |a Sasaki, Jiei |0 (orcid)0000-0002-5129-2336 |4 aut | |
| 700 | 1 | |a Sumita, Hiromi |4 aut | |
| 700 | 1 | |a Ito, Jumpei |4 aut | |
| 700 | 1 | |a Maenaka, Katsumi |0 (orcid)0000-0002-5459-521X |4 aut | |
| 700 | 1 | |a Sato, Kei |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2024) vom: 22. März |
| 773 | 1 | 8 | |g year:2024 |g day:22 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-4106877/v1 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 22 |c 03 | ||