文章基本信息

标题：Affimer proteins inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action
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作者：James I. Robinson ; Euan W. Baxter ; Robin L. Owen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：1
页码：E72-E81
DOI：10.1073/pnas.1707856115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：Fc gamma receptor IIIa ; specific inhibitor ; Affimer ; allosteric ; competitive