9PRU

Complex of the 3G8 Fab bound to Fc gamma receptor 3a / CD16a F158 allotype

Summary for 9PRU

• Entry DOI: 10.2210/pdb9pru/pdb
• Descriptor: 3G8 Fab light chain, 3G8 Fab Heavy Chain, Low affinity immunoglobulin gamma Fc region receptor III-A, ... (10 entities in total)
• Functional Keywords: antigen-binding fragment fc gamma receptor n-glycan glycoprotein, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 12
• Total formula weight: 274447.13

Authors

Barb, A.W.,Lanzilotta, W.N.,Kremer, P.G. (deposition date: 2025-07-24, release date: 2025-12-31)

Primary citation

Kremer, P.G.,Tolbert, W.D.,Gazaway, E.,Hernandez, B.G.,Korzeniowski, M.K.,Dyba, Z.A.,Grelsson, T.,Grant, O.C.,Lanzilotta, W.N.,Pazgier, M.,Woods, R.J.,Barb, A.W.
The impact of N-glycan conformational entropy on the binding affinity of Fc gamma receptor IIIa/CD16a.
Structure, 2025

PubMed Abstract: The affinity of Fc γ receptor IIIa (FcγRIIIa) binding to immunoglobulin G1 (IgG1) correlates with patient responses for antibody-based therapeutics. Among multiple factors affecting affinity, a mechanism defining how the composition of the FcγRIIIa N162 glycan regulates affinity remains undefined. Here, we evaluate the binding modes of two competitive FcγRIIIa ligands. IgG1 Fc binding is sensitive to N162 glycan composition, unlike the antigen-binding fragment (Fab) of the FcγRIII-specific antibody 3G8. Both ligands bound to overlapping surfaces, utilizing different angles of attack such that the IgG1 Fc but not 3G8 Fab limited the space available to the FcγRIII N162 N-glycan. FcγRIII binding to IgG1 Fc generated a 2.1 kcal/mol penalty from a loss of N162 glycan conformational entropy, greater than the 0.3 kcal/mol penalty for 3G8 and consistent with binding measurements. Thus, the conformational entropy of the FcγRIIIa N162-glycan is the predominant force modulating differential binding affinity compared to 3G8 Fab binding for endogenous FcγRIIIa glycoforms.

PubMed: 41421343
DOI: 10.1016/j.str.2025.11.015

Experimental method

X-RAY DIFFRACTION (1.9 Å)