National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI127521
米国
引用
ジャーナル: Commun Biol / 年: 2023 タイトル: SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode. 著者: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / ...著者: Jule Goike / Ching-Lin Hsieh / Andrew P Horton / Elizabeth C Gardner / Ling Zhou / Foteini Bartzoka / Nianshuang Wang / Kamyab Javanmardi / Andrew Herbert / Shawn Abbassi / Xuping Xie / Hongjie Xia / Pei-Yong Shi / Rebecca Renberg / Thomas H Segall-Shapiro / Cynthia I Terrace / Wesley Wu / Raghav Shroff / Michelle Byrom / Andrew D Ellington / Edward M Marcotte / James M Musser / Suresh V Kuchipudi / Vivek Kapur / George Georgiou / Scott C Weaver / John M Dye / Daniel R Boutz / Jason S McLellan / Jimmy D Gollihar / 要旨: The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations ...The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.
分子量: 14455.997 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
#3: 抗体
N3-1Fablightchain
分子量: 11828.046 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Homo sapiens (ヒト)
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実験情報
-
実験
実験
手法: 電子顕微鏡法
EM実験
試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法
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試料調製
構成要素
ID
名称
タイプ
Entity ID
Parent-ID
由来
1
The complex of N3-1 Fab bound to two receptor binding domains of the spike
COMPLEX
all
0
MULTIPLESOURCES
2
Spikeglycoprotein
COMPLEX
#1
1
RECOMBINANT
3
N3-1 Fab
COMPLEX
#2-#3
1
RECOMBINANT
由来(天然)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
2
Severe acute respiratory syndrome coronavirus 2 (ウイルス)
2697049
3
3
Homo sapiens (ヒト)
9606
由来(組換発現)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
2
Homo sapiens (ヒト)
9606
3
3
Homo sapiens (ヒト)
9606
緩衝液
pH: 8 / 詳細: 2 mM Tris pH 8.0, 200 mM NaCl, 0.02% NaN3
試料
濃度: 0.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Collected on UltrAuFoil 1.2-1.3 with 0.2 mg/mL HexaPro and 5x fold molar excess FabN3-1 spiked in 30 minutes before freezing.
試料支持
グリッドの材料: GOLD / グリッドのタイプ: UltrAuFoil R1.2/1.3
急速凍結
装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 295 K