ジャーナル: Nat Commun / 年: 2023 タイトル: Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2. 著者: Kuan-Ying A Huang / Xiaorui Chen / Arpita Mohapatra / Hong Thuy Vy Nguyen / Lisa Schimanski / Tiong Kit Tan / Pramila Rijal / Susan K Vester / Rory A Hills / Mark Howarth / Jennifer R Keeffe ...著者: Kuan-Ying A Huang / Xiaorui Chen / Arpita Mohapatra / Hong Thuy Vy Nguyen / Lisa Schimanski / Tiong Kit Tan / Pramila Rijal / Susan K Vester / Rory A Hills / Mark Howarth / Jennifer R Keeffe / Alexander A Cohen / Leesa M Kakutani / Yi-Min Wu / Md Shahed-Al-Mahmud / Yu-Chi Chou / Pamela J Bjorkman / Alain R Townsend / Che Ma / 要旨: Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural ...Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the "down" state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses. We observed a continuum of partially overlapping antibody epitopes from lower to upper part of the inner face of the RBD and some antibodies extend towards the receptor-binding motif. The majority of antibodies are substantially compromised by three mutational hotspots (S371L/F, S373P and S375F) in the lower part of the Omicron BA.1, BA.2 and BA.4/5 RBD. By contrast, antibody IY-2A induces a partial unfolding of this variable region and interacts with a conserved conformational epitope to tolerate all antigenic variations and neutralize diverse sarbecoviruses as well. This finding establishes that antibody recognition is not limited to the normal surface structures on the RBD. In conclusion, the delineation of functionally and structurally conserved RBD epitopes highlights potential vaccine and therapeutic candidates for COVID-19.
全体 : Complex of Delta Spike and IS-9A with two Fabs bound to one Spike...
全体
名称: Complex of Delta Spike and IS-9A with two Fabs bound to one Spike in 3-RBD-up conformation
要素
複合体: Complex of Delta Spike and IS-9A with two Fabs bound to one Spike in 3-RBD-up conformation
複合体: IS-9A Fab
タンパク質・ペプチド: IS-9A Fab heavy chain
タンパク質・ペプチド: IS-9A Fab light chain
複合体: Spike glycoprotein
タンパク質・ペプチド: Spike glycoprotein
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Complex of Delta Spike and IS-9A with two Fabs bound to one Spike...
超分子
名称: Complex of Delta Spike and IS-9A with two Fabs bound to one Spike in 3-RBD-up conformation タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: #1-#3