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Structure paper

TitleA trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 2, Page 202-209, Year 2021
Publish dateJan 11, 2021
AuthorsTianshu Xiao / Jianming Lu / Jun Zhang / Rebecca I Johnson / Lindsay G A McKay / Nadia Storm / Christy L Lavine / Hanqin Peng / Yongfei Cai / Sophia Rits-Volloch / Shen Lu / Brian D Quinlan / Michael Farzan / Michael S Seaman / Anthony Griffiths / Bing Chen /
PubMed AbstractEffective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves ...Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
External linksNat Struct Mol Biol / PubMed:33432247 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 3.7 Å
Structure data

EMDB-22891, PDB-7kj2:
SARS-CoV-2 Spike Glycoprotein with one ACE2 Bound
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-22892, PDB-7kj3:
SARS-CoV-2 Spike Glycoprotein with two ACE2 Bound
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-22893, PDB-7kj4:
SARS-CoV-2 Spike Glycoprotein with three ACE2 Bound
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-22894, PDB-7kj5:
SARS-CoV-2 Spike Glycoprotein, prefusion with one RBD up conformation
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

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

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/HYDROLASE / VIRAL PROTEIN / VIRAL PROTEIN-HYDROLASE complex

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