| Structural highlights
9pru is a 12 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| 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
The affinity of Fc gamma receptor IIIa (FcgammaRIIIa) 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 FcgammaRIIIa N162 glycan regulates affinity remains undefined. Here, we evaluate the binding modes of two competitive FcgammaRIIIa ligands. IgG1 Fc binding is sensitive to N162 glycan composition, unlike the antigen-binding fragment (Fab) of the FcgammaRIII-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 FcgammaRIII N162 N-glycan. FcgammaRIII 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 FcgammaRIIIa N162-glycan is the predominant force modulating differential binding affinity compared to 3G8 Fab binding for endogenous FcgammaRIIIa glycoforms.
The impact of N-glycan conformational entropy on the binding affinity of Fc gamma receptor IIIa/CD16a.,Kremer PG, Tolbert WD, Gazaway E, Hernandez BG, Korzeniowski MK, Dyba ZA, Grelsson T, Grant OC, Lanzilotta WN, Pazgier M, Woods RJ, Barb AW Structure. 2025 Dec 19:S0969-2126(25)00475-7. doi: 10.1016/j.str.2025.11.015. PMID:41421343[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
- ↑ Kremer PG, Tolbert WD, Gazaway E, Hernandez BG, Korzeniowski MK, Dyba ZA, Grelsson T, Grant OC, Lanzilotta WN, Pazgier M, Woods RJ, Barb AW. The impact of N-glycan conformational entropy on the binding affinity of Fc γ receptor IIIa/CD16a. Structure. 2025 Dec 19:S0969-2126(25)00475-7. PMID:41421343 doi:10.1016/j.str.2025.11.015
|
