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-Structure paper
タイトル | D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction. |
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ジャーナル・号・ページ | Cell Rep, Vol. 34, Issue 2, Page 108630, Year 2021 |
掲載日 | 2021年1月12日 |
著者 | Sophie M-C Gobeil / Katarzyna Janowska / Shana McDowell / Katayoun Mansouri / Robert Parks / Kartik Manne / Victoria Stalls / Megan F Kopp / Rory Henderson / Robert J Edwards / Barton F Haynes / Priyamvada Acharya / |
PubMed 要旨 | The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, ...The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryoelectron microscopy (cryo-EM) structures reveal altered receptor binding domain (RBD) disposition; antigenicity and proteolysis experiments reveal structural changes and enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the up/down ratio of the RBDs in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, which harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 S conformational landscape and allostery and have implications for vaccine design. |
リンク | Cell Rep / PubMed:33417835 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.84 Å |
構造データ | EMDB-22821, PDB-7kdg: EMDB-22822, PDB-7kdh: EMDB-22823, PDB-7kdi: EMDB-22824, PDB-7kdj: EMDB-22825, PDB-7kdk: EMDB-22826, PDB-7kdl: EMDB-22831, PDB-7ke4: EMDB-22832, PDB-7ke6: EMDB-22833, PDB-7ke7: EMDB-22834, PDB-7ke8: EMDB-22835, PDB-7ke9: EMDB-22836, PDB-7kea: EMDB-22837, PDB-7keb: EMDB-22838, PDB-7kec: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / SARS-CoV-2 Spike Protein Trimer |