5mn2
From Proteopedia
Cocrystal structure of Fc gamma receptor IIIa interacting with Affimer G3, a specific binding protein which blocks IgG binding to the receptor.
Structural highlights
Disease[FCG3A_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.[1] [2] [3] [4] Function[FCG3A_HUMAN] Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.[5] [6] Publication Abstract from PubMedProtein-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 (FcgammaRs). High sequence identity (98%) between the genes encoding FcgammaRIIIa (expressed on macrophages and natural killer cells) and FcgammaRIIIb (expressed on neutrophils) has prevented the development of monospecific agents against these therapeutic targets. We now report the identification of FcgammaRIIIa-specific artificial binding proteins called "Affimer" that block IgG binding and abrogate FcgammaRIIIa-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. Affimer proteins inhibit immune complex binding to FcgammaRIIIa with high specificity through competitive and allosteric modes of action.,Robinson JI, Baxter EW, Owen RL, Thomsen M, Tomlinson DC, Waterhouse MP, Win SJ, Nettleship JE, Tiede C, Foster RJ, Owens RJ, Fishwick CWG, Harris SA, Goldman A, McPherson MJ, Morgan AW Proc Natl Acad Sci U S A. 2017 Dec 15. pii: 1707856115. doi:, 10.1073/pnas.1707856115. PMID:29247053[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Synthetic construct sequences | Baxter, E W | Goldman, A | Harris, S A | McPherson, M J | Morgan, A W | Nettleship, J E | Owen, R L | Owens, R J | Robinson, J I | Thomsen, M | Tiede, C | Tomlinson, D C | Waterhouse, M P | Fc gamma receptor iiia affimer allosteric inhibitor fcgr3a | Immune system
