10FJ

FcgRIIa in complex with IV.3 Fab

Summary for 10FJ

• Entry DOI: 10.2210/pdb10fj/pdb
• EMDB information: 75133
• Descriptor: Low affinity immunoglobulin gamma Fc region receptor II-a, IV.3 Fab heavy chain, IV.3 Fab light chain (3 entities in total)
• Functional Keywords: platelet, fcgriia, mab iv.3, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 71950.78

Authors

Coller, B.S.,Wang, J.L. (deposition date: 2026-01-16, release date: 2026-07-01)

Primary citation

Wang, J.,Novack, S.,Li, J.,Niejadlik, E.G.,Bournazos, S.,Coller, B.S.,Filizola, M.
Mechanistic Basis for the Selective Recognition of the Fc gamma Receptor IIa by Monoclonal Antibody IV.3.
Biorxiv, 2026

PubMed Abstract: The monoclonal antibody IV.3 selectively binds the platelet Fcγ receptor IIa (FcγRIIa), potently blocking immune complex engagement without cross-reacting with the closely-related FcγRIIb. This specificity has made IV.3 invaluable for dissecting FcγRIIa-mediated activation in diverse conditions, including infection, autoimmunity, thromboinflammation, and platelet-mediated thrombosis. We combined cryogenic electron microscopy, surface plasmon resonance, alchemical free energy calculations, and molecular dynamics simulations to elucidate IV.3's binding sites on FcγRIIa and the mechanistic basis of IV.3 specificity. We find that IV.3 engages a broader FcγRIIa epitope than previously recognized, extending beyond residues H/R134 and L135 (R and S in FcγRIIb). Simulations of FcγIIa-R134 variants bearing either L135 or S135 reveal that IV.3 specificity arises from hydrophobic stabilization mediated by L135 and disruption of an R134-specific interaction network in the presence of S135. These findings provide a mechanistic framework for rational design of FcγRIIa-targeted therapeutics.

PubMed: 41867816
DOI: 10.64898/2026.03.05.709909

Experimental method

ELECTRON MICROSCOPY (3.5 Å)