5ML9

Cocrystal structure of Fc gamma receptor IIIa interacting with Affimer F4, a specific binding protein which blocks IgG binding to the receptor.

5ML9 の概要

• エントリーDOI: 10.2210/pdb5ml9/pdb
• 分子名称: Low affinity immunoglobulin gamma Fc region receptor III-A, Affimer F4 with specificity for Fc gamma receptor IIIa, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: fc gamma receptor iiia affimer competitive inhibitor fcgr3a, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34676.97

構造登録者

Robinson, J.I.,Tomlinson, D.C.,Baxter, E.W.,Owen, R.L.,Thomsen, M.,Win, S.J.,Nettleship, J.E.,Tiede, C.,Foster, R.J.,Waterhouse, M.P.,Harris, S.A.,Owens, R.J.,Fishwick, C.W.G.,Goldman, A.,McPherson, M.J.,Morgan, A.W. (登録日: 2016-12-06, 公開日: 2017-12-13, 最終更新日: 2024-10-23)

主引用文献

Robinson, J.I.,Baxter, E.W.,Owen, R.L.,Thomsen, M.,Tomlinson, D.C.,Waterhouse, M.P.,Win, S.J.,Nettleship, J.E.,Tiede, C.,Foster, R.J.,Owens, R.J.,Fishwick, C.W.G.,Harris, S.A.,Goldman, A.,McPherson, M.J.,Morgan, A.W.
Affimer proteins inhibit immune complex binding to Fc gamma RIIIa with high specificity through competitive and allosteric modes of action.
Proc. Natl. Acad. Sci. U.S.A., 115:E72-E81, 2018

PubMed Abstract: Protein-protein interactions are essential for the control of cellular functions and are critical for regulation of the immune system. One example is the binding of Fc regions of IgG to the Fc gamma receptors (FcγRs). High sequence identity (98%) between the genes encoding FcγRIIIa (expressed on macrophages and natural killer cells) and FcγRIIIb (expressed on neutrophils) has prevented the development of monospecific agents against these therapeutic targets. We now report the identification of FcγRIIIa-specific artificial binding proteins called "Affimer" that block IgG binding and abrogate FcγRIIIa-mediated downstream effector functions in macrophages, namely TNF release and phagocytosis. Cocrystal structures and molecular dynamics simulations have revealed the structural basis of this specificity for two Affimer proteins: One binds directly to the Fc binding site, whereas the other acts allosterically.

PubMed: 29247053
DOI: 10.1073/pnas.1707856115

実験手法

X-RAY DIFFRACTION (2.35 Å)