7KN7

Crystal structure of SARS-CoV-2 receptor binding domain complexed with nanobody VHH W and antibody Fab CC12.3

7KN7 の概要

• エントリーDOI: 10.2210/pdb7kn7/pdb
• 分子名称: Spike protein S1, VHH W, CC12.3 Fab heavy chain, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, nanobody, spike, coronavirus, covid-19, immune system, nanobody-antigen complex, single-domain antibody, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 88311.22

構造登録者

Liu, H.,Yuan, M.,Zhu, X.,Wu, N.C.,Wilson, I.A. (登録日: 2020-11-04, 公開日: 2021-01-20, 最終更新日: 2024-11-06)

主引用文献

Koenig, P.A.,Das, H.,Liu, H.,Kummerer, B.M.,Gohr, F.N.,Jenster, L.M.,Schiffelers, L.D.J.,Tesfamariam, Y.M.,Uchima, M.,Wuerth, J.D.,Gatterdam, K.,Ruetalo, N.,Christensen, M.H.,Fandrey, C.I.,Normann, S.,Todtmann, J.M.P.,Pritzl, S.,Hanke, L.,Boos, J.,Yuan, M.,Zhu, X.,Schmid-Burgk, J.L.,Kato, H.,Schindler, M.,Wilson, I.A.,Geyer, M.,Ludwig, K.U.,Hallberg, B.M.,Wu, N.C.,Schmidt, F.I.
Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape.
Science, 371:-, 2021

PubMed Abstract: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. In this study, we generated four neutralizing nanobodies that target the receptor binding domain of the SARS-CoV-2 spike protein. We used x-ray crystallography and cryo-electron microscopy to define two distinct binding epitopes. On the basis of these structures, we engineered multivalent nanobodies with more than 100 times the neutralizing activity of monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor binding competition, whereas other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion and rendered the virions noninfectious.

PubMed: 33436526
DOI: 10.1126/science.abe6230

実験手法

X-RAY DIFFRACTION (2.73 Å)