7URU

Crystal structure of the low affinity Fc gamma receptor IIIA variant in complex with the Fc of IgG1.

7URU の概要

• エントリーDOI: 10.2210/pdb7uru/pdb
• 分子名称: Immunoglobulin gamma-1 heavy chain, Low affinity immunoglobulin gamma Fc region receptor III-A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: receptor complex, fc receptor, antibody, immune system, igg1, cd16
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 73826.58

構造登録者

Tolbert, W.D.,Pazgier, M. (登録日: 2022-04-22, 公開日: 2023-04-26, 最終更新日: 2025-12-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)