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TitleStructural impact on SARS-CoV-2 spike protein by D614G substitution.
Journal, issue, pagesScience, Vol. 372, Issue 6541, Page 525-530, Year 2021
Publish dateApr 30, 2021
AuthorsJun Zhang / Yongfei Cai / Tianshu Xiao / Jianming Lu / Hanqin Peng / Sarah M Sterling / Richard M Walsh / Sophia Rits-Volloch / Haisun Zhu / Alec N Woosley / Wei Yang / Piotr Sliz / Bing Chen /
PubMed AbstractSubstitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. ...Substitution for aspartic acid (D) by glycine (G) at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. Here, we report cryo-electron microscopy structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations that differ primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer-effectively increasing the number of functional spikes and enhancing infectivity-and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.
External linksScience / PubMed:33727252 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.5 Å
Structure data

EMDB-23010, PDB-7krq:
Structural impact on SARS-CoV-2 spike protein by D614G substitution
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-23011, PDB-7krr:
Structural impact on SARS-CoV-2 spike protein by D614G substitution
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-23012, PDB-7krs:
Structural impact on SARS-CoV-2 spike protein by D614G substitution
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

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

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsACE2 protein, human / Amino Acid Substitution / Angiotensin-Converting Enzyme 2 / Antibodies, Viral / COVID-19 / Cryoelectron Microscopy / Humans / Hydrophobic and Hydrophilic Interactions / Models, Molecular / Mutant Proteins / Protein Binding / Protein Conformation / Protein Domains / Protein Subunits / Receptors, Coronavirus / SARS-CoV-2 / Spike Glycoprotein, Coronavirus / Virus Internalization / spike protein, SARS-CoV-2 / VIRAL PROTEIN

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