9TVT

CRYSTAL STRUCTURE OF SARS-COV-2 RECEPTOR BINDING DOMAIN (RBD-beta variant) in complex with 3D2 Fab and 1D1 Fab

Summary for 9TVT

• Entry DOI: 10.2210/pdb9tvt/pdb
• Descriptor: Spike protein S1, 1D1 FAB HEAVY CHAIN, 1D1 FAB LIGHT CHAIN, ... (9 entities in total)
• Functional Keywords: antibody, virus, complex, sars-cov-2, viral protein complex, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 10
• Total formula weight: 241396.58

Authors

Welin, M.,Cicek, H.,Focht, D.,Kimbung, Y.R.,Pisitkun, T. (deposition date: 2026-01-13, release date: 2026-07-15)

Primary citation

Pianpaktr, P.,Ramanandana, P.,Nanthawong, S.,Wongtangprasert, T.,Saelao, P.,Muanwien, P.,Boonkrai, C.,Cicek, H.,Focht, D.,Kimbung, R.,Welin, M.,Stahl, V.L.,Graban, E.M.,Vachet, R.W.,Pisitkun, T.,Limpikirati, P.K.
Mass spectrometry-based mapping of conformational epitopes on SARS-CoV-2 antigens targeted by monoclonal antibodies.
Int.J.Biol.Macromol., 372:153102-153102, 2026

PubMed Abstract: The spike glycoprotein of SARS-CoV-2, particularly its receptor-binding domain (RBD), is a key target for therapeutic monoclonal antibodies (mAbs). Epitope mapping is therefore critical for the development of effective antiviral therapeutics. In this study, diethylpyrocarbonate covalent labeling mass spectrometry (DEPC CL-MS) was applied to map epitopes on the beta (B.1.351) and omicron (B.1.1.529) variants of the SARS-CoV-2 RBD, as well as on the original SARS-CoV-2 spike S subunit, in complex with anti-SARS-CoV-2 mAbs. Combined with bottom-up LC-MS/MS, DEPC labeling enabled site-specific identification of residues exhibiting significant modification changes. Clustering of these residues on the protein surface identified potential epitopes for the 1D1 mAb on the RBDs and for the 1D3 mAb on the C-terminal domain of the S subunit. Structural interpretation was supported by available experimental data, with AlphaFold models providing supplementary context where needed. Thus, "theory guides, but experiment decides": AlphaFold aided epitope identification when high-resolution antigen-antibody complex structures were unavailable, but conclusions were ultimately resolved experimentally. Together, these findings establish DEPC CL-MS as a useful and complementary approach for epitope mapping, providing residue-level insights into antigen-antibody interactions and advancing structural understanding for antiviral mAb development.

PubMed: 42324012
DOI: 10.1016/j.ijbiomac.2026.153102

Experimental method

X-RAY DIFFRACTION (2.85 Å)