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Structure paper

TitleStructures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.
Journal, issue, pagesScience, Vol. 375, Issue 6584, Page 1048-1053, Year 2022
Publish dateMar 4, 2022
AuthorsWanchao Yin / Youwei Xu / Peiyu Xu / Xiaodan Cao / Canrong Wu / Chunyin Gu / Xinheng He / Xiaoxi Wang / Sijie Huang / Qingning Yuan / Kai Wu / Wen Hu / Zifu Huang / Jia Liu / Zongda Wang / Fangfang Jia / Kaiwen Xia / Peipei Liu / Xueping Wang / Bin Song / Jie Zheng / Hualiang Jiang / Xi Cheng / Yi Jiang / Su-Jun Deng / H Eric Xu /
PubMed AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.
External linksScience / PubMed:35133176 / PubMed Central
MethodsEM (single particle)
Resolution2.47 - 3.18 Å
Structure data

EMDB-32679, PDB-7wp9:
SARS-CoV-2 Omicron Variant SPIKE trimer, all RBDs down
Method: EM (single particle) / Resolution: 2.56 Å

EMDB-32680, PDB-7wpa:
SARS-CoV-2 Omicron Variant SPIKE trimer complexed with ACE2
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-32681, PDB-7wpb:
SARS-CoV-2 Omicron Variant RBD complexed with ACE2
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-32682, PDB-7wpc:
The second RBD of SARS-CoV-2 Omicron Variant in complexed with RBD-ACE2
Method: EM (single particle) / Resolution: 2.57 Å

EMDB-32683, PDB-7wpd:
SARS-CoV-2 Omicron Variant S Trimer complexed with one JMB2002 Fab
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-32684, PDB-7wpe:
SARS-CoV-2 Omicron Variant S Trimer complexed with two JMB2002 Fab
Method: EM (single particle) / Resolution: 2.69 Å

EMDB-32685, PDB-7wpf:
SARS-CoV-2 Omicron Variant S Trimer complexed with three JMB2002 Fab
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-32736, PDB-7wrv:
The interface of JMB2002 Fab binds to SARS-CoV-2 Omicron Variant S
Method: EM (single particle) / Resolution: 2.47 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CL:
Unknown entry / Chloride

ChemComp-ZN:
Unknown entry

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • mus musculus (house mouse)
  • lama glama (llama)
  • Severe acute respiratory syndrome coronavirus
KeywordsVIRAL PROTEIN / RBD / SARS-CoV-2 / Omicron / S / Trimer / Fab / Antibody

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