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(New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...) |
(Structural Basis of SARS-CoV-2 Omicron Immune Evasion and Receptor Engagement (Science, 2022; structure represented by PDB: 7Y9Z) The rapid global spread of the SARS-CoV-2 Omicron variant raised urge) |
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| - | == | + | == SARS-CoV-2 Omicron Spike Glycoprotein (PDB: 7Y9Z) == |
| - | <StructureSection load=' | + | |
| - | + | <StructureSection load='7Y9Z' size='380' side='right' caption='Cryo-EM structure of the SARS-CoV-2 Omicron spike (PDB: 7Y9Z).' scene='Spike_Trimer_Overview'> | |
| - | + | The Omicron variant of SARS-CoV-2 emerged in late 2021 with an unusually high number of mutations in the spike glycoprotein, raising global concerns about increased transmissibility, vaccine breakthrough infections, and reduced antibody neutralization. The cryo-electron microscopy structure represented by '''PDB ID: 7Y9Z''' provides crucial insights into the molecular basis of Omicron’s immune evasion and its sustained ability to bind the human ACE2 receptor.<ref name="McCallum2022">McCallum M, Czudnochowski N, Rosen LE, Zepeda SK, Bowen JE, Walls AC, Hauser K, Joshi A, Stewart C, Dillen JR, et al. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. <i>Science</i>. 2022 Feb 25;375(6583):864–868. doi:10.1126/science.abn8652.</ref> | |
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| + | The spike protein is a trimeric Class I fusion protein composed of S1 and S2 subunits. S1 contains the receptor-binding domain (RBD), which alternates between “up” and “down” conformations. Omicron introduces more than 30 mutations across the spike, many concentrated in the RBD. These changes modify the antigenic surface, weaken the binding of multiple classes of neutralizing antibodies, and reshape epitopes targeted by prior infection or vaccine-induced immunity.<ref name="McCallum2022" /> | ||
| + | </StructureSection> | ||
== Function == | == Function == | ||
| + | The spike protein mediates viral entry by recognizing and binding to the host cell receptor ACE2. Upon receptor engagement, conformational changes in the S2 region drive membrane fusion. Omicron preserves this essential function while altering residue interactions that enhance ACE2 affinity. Key mutations—including Q493R, Q498R, and N501Y—generate new hydrogen bonds and electrostatic contacts, increasing binding strength and contributing to high infectivity. <ref name="McCallum2022" /> | ||
== Disease == | == Disease == | ||
| + | Omicron is responsible for multiple global infection waves due to its immune-evasive spike architecture. Structural alterations significantly reduce neutralization by monoclonal antibodies and convalescent or vaccine-elicited sera. This explains breakthrough infections and the reduced efficacy of several therapeutic antibody cocktails. <ref name="McCallum2022" /> | ||
== Relevance == | == Relevance == | ||
| + | Understanding the Omicron spike structure guides the development of improved vaccines and broad-spectrum therapeutic antibodies. Mapping mutation-induced structural changes informs future variant surveillance and antiviral design. <ref name="McCallum2022" /> | ||
== Structural highlights == | == Structural highlights == | ||
| + | * '''Omicron RBD mutations''' (e.g., G446S, S477N, T478K, E484A, Q493R, Q498R, N501Y, Y505H) remodel epitopes and disrupt antibody binding. <ref name="McCallum2022" /> | ||
| + | * '''ACE2-binding residues''' are optimized, strengthening receptor affinity despite widespread antigenic changes. <ref name="McCallum2022" /> | ||
| + | * The RBD exhibits a bias toward the '''“up” conformation''', increasing exposure to ACE2 while shielding neutralizing sites. <ref name="McCallum2022" /> | ||
| - | + | === Interactive Scenes === | |
| + | * <scene name="Spike_Trimer_Overview">Omicron spike trimer overview</scene> | ||
| + | * <scene name="RBD_Omicron_Mutations">RBD mutation landscape and immune evasion</scene> | ||
| + | * <scene name="ACE2_Interface">ACE2-binding residues enhanced in Omicron</scene> | ||
| - | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Contents |
SARS-CoV-2 Omicron Spike Glycoprotein (PDB: 7Y9Z)
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Function
The spike protein mediates viral entry by recognizing and binding to the host cell receptor ACE2. Upon receptor engagement, conformational changes in the S2 region drive membrane fusion. Omicron preserves this essential function while altering residue interactions that enhance ACE2 affinity. Key mutations—including Q493R, Q498R, and N501Y—generate new hydrogen bonds and electrostatic contacts, increasing binding strength and contributing to high infectivity. [1]
Disease
Omicron is responsible for multiple global infection waves due to its immune-evasive spike architecture. Structural alterations significantly reduce neutralization by monoclonal antibodies and convalescent or vaccine-elicited sera. This explains breakthrough infections and the reduced efficacy of several therapeutic antibody cocktails. [1]
Relevance
Understanding the Omicron spike structure guides the development of improved vaccines and broad-spectrum therapeutic antibodies. Mapping mutation-induced structural changes informs future variant surveillance and antiviral design. [1]
Structural highlights
- Omicron RBD mutations (e.g., G446S, S477N, T478K, E484A, Q493R, Q498R, N501Y, Y505H) remodel epitopes and disrupt antibody binding. [1]
- ACE2-binding residues are optimized, strengthening receptor affinity despite widespread antigenic changes. [1]
- The RBD exhibits a bias toward the “up” conformation, increasing exposure to ACE2 while shielding neutralizing sites. [1]
