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5mn2

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Revision as of 17:40, 8 November 2023

Cocrystal structure of Fc gamma receptor IIIa interacting with Affimer G3, a specific binding protein which blocks IgG binding to the receptor.

Structural highlights

5mn2 is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.35Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

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 (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

↑ Grier JT, Forbes LR, Monaco-Shawver L, Oshinsky J, Atkinson TP, Moody C, Pandey R, Campbell KS, Orange JS. Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J Clin Invest. 2012 Oct 1;122(10):3769-80. doi: 10.1172/JCI64837. Epub 2012 Sep, 24. PMID:23006327 doi:http://dx.doi.org/10.1172/JCI64837
↑ Jawahar S, Moody C, Chan M, Finberg R, Geha R, Chatila T. Natural Killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II). Clin Exp Immunol. 1996 Mar;103(3):408-13. PMID:8608639
↑ de Haas M, Koene HR, Kleijer M, de Vries E, Simsek S, van Tol MJ, Roos D, von dem Borne AE. A triallelic Fc gamma receptor type IIIA polymorphism influences the binding of human IgG by NK cell Fc gamma RIIIa. J Immunol. 1996 Apr 15;156(8):2948-55. PMID:8609432
↑ de Vries E, Koene HR, Vossen JM, Gratama JW, von dem Borne AE, Waaijer JL, Haraldsson A, de Haas M, van Tol MJ. Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. Blood. 1996 Oct 15;88(8):3022-7. PMID:8874200
↑ Ferrara C, Grau S, Jager C, Sondermann P, Brunker P, Waldhauer I, Hennig M, Ruf A, Rufer AC, Stihle M, Umana P, Benz J. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between Fc{gamma}RIII and antibodies lacking core fucose. Proc Natl Acad Sci U S A. 2011 Jul 18. PMID:21768335 doi:10.1073/pnas.1108455108
↑ Mizushima T, Yagi H, Takemoto E, Shibata-Koyama M, Isoda Y, Iida S, Masuda K, Satoh M, Kato K. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells. 2011 Nov;16(11):1071-1080. doi:, 10.1111/j.1365-2443.2011.01552.x. PMID:22023369 doi:10.1111/j.1365-2443.2011.01552.x
↑ 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. Affimer proteins inhibit immune complex binding to FcgammaRIIIa with high specificity through competitive and allosteric modes of action. Proc Natl Acad Sci U S A. 2017 Dec 15. pii: 1707856115. doi:, 10.1073/pnas.1707856115. PMID:29247053 doi:http://dx.doi.org/10.1073/pnas.1707856115

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mn2"

@@ Line 1: / Line 1: @@
 ==Cocrystal structure of Fc gamma receptor IIIa interacting with Affimer G3, a specific binding protein which blocks IgG binding to the receptor.==
-<StructureSection load='5mn2' size='340' side='right' caption='[[5mn2]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='5mn2' size='340' side='right'caption='[[5mn2]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mn2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MN2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mn2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MN2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FCGR3A, CD16A, FCG3, FCGR3, IGFR3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mn2 OCA], [http://pdbe.org/5mn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mn2 RCSB], [http://www.ebi.ac.uk/pdbsum/5mn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mn2 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mn2 OCA], [https://pdbe.org/5mn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mn2 RCSB], [https://www.ebi.ac.uk/pdbsum/5mn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mn2 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/FCG3A_HUMAN FCG3A_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23006327</ref> <ref>PMID:8608639</ref> <ref>PMID:8609432</ref> <ref>PMID:8874200</ref>
+[https://www.uniprot.org/uniprot/FCG3A_HUMAN FCG3A_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23006327</ref> <ref>PMID:8608639</ref> <ref>PMID:8609432</ref> <ref>PMID:8874200</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/FCG3A_HUMAN 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.<ref>PMID:21768335</ref> <ref>PMID:22023369</ref>
+[https://www.uniprot.org/uniprot/FCG3A_HUMAN 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.<ref>PMID:21768335</ref> <ref>PMID:22023369</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Synthetic construct sequences]]
+[[Category: Large Structures]]
-[[Category: Baxter, E W]]
+[[Category: Synthetic construct]]
-[[Category: Goldman, A]]
+[[Category: Baxter EW]]
-[[Category: Harris, S A]]
+[[Category: Goldman A]]
-[[Category: McPherson, M J]]
+[[Category: Harris SA]]
-[[Category: Morgan, A W]]
+[[Category: McPherson MJ]]
-[[Category: Nettleship, J E]]
+[[Category: Morgan AW]]
-[[Category: Owen, R L]]
+[[Category: Nettleship JE]]
-[[Category: Owens, R J]]
+[[Category: Owen RL]]
-[[Category: Robinson, J I]]
+[[Category: Owens RJ]]
-[[Category: Thomsen, M]]
+[[Category: Robinson JI]]
-[[Category: Tiede, C]]
+[[Category: Thomsen M]]
-[[Category: Tomlinson, D C]]
+[[Category: Tiede C]]
-[[Category: Waterhouse, M P]]
+[[Category: Tomlinson DC]]
-[[Category: Fc gamma receptor iiia affimer allosteric inhibitor fcgr3a]]
+[[Category: Waterhouse MP]]
-[[Category: Immune system]]

5mn2

From Proteopedia

Revision as of 17:40, 8 November 2023

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

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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