SARS-CoV-2 RBD
The receptor-binding domain (RBD) of SARS-CoV-2 spike protein is the primary target for neutralizing antibodies and vaccine development.
SARS-CoV-2 RBD
Function
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a critical component of the virus’s machinery for cell entry. Located within the S1 subunit of the spike protein, the RBD directly binds to the human ACE2 (angiotensin-converting enzyme 2) receptor on host cells, initiating viral entry. This ~25 kDa domain undergoes conformational changes that expose the receptor-binding motif (RBM), allowing high-affinity binding to ACE2.
Viral Entry Mechanism
Binding and Entry Process
- Initial Binding: RBD binds to ACE2 on target cells (lungs, kidneys, heart, etc.)
- Conformational Change: Spike protein undergoes structural rearrangements
- Membrane Fusion: S2 subunit mediates fusion of viral and cellular membranes
- Viral Entry: Viral RNA enters the host cell for replication
Key Structural Features
- Receptor-Binding Motif (RBM): Direct contact region with ACE2
- Core Domain: Provides structural stability
- Flexible Loops: Allow conformational dynamics for receptor binding
- Glycosylation Sites: Shield antigenic sites and modulate immunity
Target Details
Protein Information
Protein Information
Organism: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Gene Name: S (Spike protein) Domain: Receptor-binding domain (RBD) Protein Family: Coronavirus spike proteins
Database References
Database References
UniProt ID: P0DTC2 NCBI Reference: YP_009724390.1 / QHD43416.1 Protein Region: Arg 319 - Phe 541 (standard) / Arg 319 - Lys 537 (variant) GenBank: MN908947.3 (reference genome)
Structural Information
Structural Information
Molecular Weight: ~25 kDa Structure: Immunoglobulin-like fold with extended loops Key Residues: Y453, L455, F456, A475, F486, N487, Y489, Q493, G496, Q498, T500, N501, G502, Y505 Receptor Interface: ~20 residues make direct contact with ACE2
Variants and Mutations
Variants and Mutations
Alpha (B.1.1.7): N501Y mutation increases ACE2 binding affinity Beta (B.1.351): K417N, E484K, N501Y mutations Gamma (P.1): K417T, E484K, N501Y mutations Delta (B.1.617.2): L452R, T478K mutations Omicron (B.1.1.529): Extensive mutations including G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H
Research Applications
Vaccine Development
- mRNA Vaccines: Primary target for Pfizer-BioNTech and Moderna vaccines
- Protein Subunit Vaccines: Recombinant RBD-based vaccines
- Viral Vector Vaccines: Target antigen for adenovirus-based vaccines
- Next-Generation Vaccines: Pan-coronavirus vaccines targeting conserved RBD regions
Therapeutic Development
- Monoclonal Antibodies: Neutralizing antibodies targeting the RBD
- Entry Inhibitors: Small molecules blocking RBD-ACE2 interaction
- Decoy Receptors: Soluble ACE2 variants that compete for RBD binding
- Peptide Inhibitors: Short peptides mimicking ACE2 binding interface
Diagnostic Applications
- Serological Assays: Detection of anti-RBD antibodies for immunity assessment
- Neutralization Assays: Measuring functional antibody responses
- Binding Assays: Screening for RBD-binding molecules
- Epidemiological Studies: Tracking infection and vaccination rates
Clinical and Research Importance
Immune Response
- Primary Target: Major target for neutralizing antibodies
- T Cell Responses: Contains multiple CD4+ and CD8+ T cell epitopes
- Immune Evasion: Mutations can reduce antibody neutralization
- Cross-Reactivity: Some antibodies cross-react with other coronavirus RBDs
Drug Development Challenges
- Variant Emergence: Mutations can escape existing therapeutics
- Resistance: Need for broadly neutralizing approaches
- Manufacturing: Production of correctly folded, stable RBD protein
- Delivery: Optimal formulations for therapeutic efficacy
Research Tools
- Binding Studies: Understanding ACE2 interaction mechanisms
- Structural Biology: High-resolution structures of RBD complexes
- Evolution Studies: Tracking viral evolution and immune escape
- Computational Modeling: Predicting variant emergence and drug resistance
SARS-CoV-2 continues to evolve, and new variants may have altered RBD sequences that affect binding properties. Always verify the specific variant sequence when designing experiments or interpreting results.
We maintain multiple variants of SARS-CoV-2 RBD in our target library, including the original Wuhan strain, major variants of concern, and recent circulating strains. Contact our team to discuss which variant is most appropriate for your research needs.