ArticleJournal of the American Chemical Society2013
Engineering hydrophobic protein-carbohydrate interactions to fine-tune monoclonal antibodies.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 85 citations in OpenAlex.
- Chemoenzymatic synthesis of unusual antibody glycoforms using E. coli expressed human and bovine β-1,4-galactosyltransferase and their mutants.Carbohydrate research · 2026Article
- ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria.Cell reports · 2025Article
- The role of antibody glycosylation in autoimmune and alloimmune kidney diseases.Nature reviews. Nephrology · 2024Review
- Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi.Scientific reports · 2022Article
- The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis.International journal of molecular sciences · 2022Article
- Rapid Antibody Glycoengineering in CHO Cells Via RNA Interference and CGE-LIF N-Glycomics.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Role ofFrontiers in immunology · 2022Article
- Enhanced Immunomodulatory Effect of Intravenous Immunoglobulin by Fc Galactosylation and Nonfucosylation.Frontiers in immunology · 2022Article
- On the Use of Surface Plasmon Resonance Biosensing to Understand IgG-FcγR Interactions.International journal of molecular sciences · 2021Review
- Solution structure of deglycosylated human IgG1 shows the role of CBiophysical journal · 2021Article
- Glycoengineering Chinese hamster ovary cells: a short history.Biochemical Society transactions · 2021Review
- Glycan-protein interactions determine kinetics ofRSC chemical biology · 2021Article
- Biophysical Evaluation of Rhesus Macaque Fc Gamma Receptors Reveals Similar IgG Fc Glycoform Preferences to Human Receptors.Frontiers in immunology · 2021Article
- Immunoglobulin G Glycosylation in Diseases.Experientia supplementum (2012) · 2021Article
- Impact of IgG1 N-glycosylation on their interaction with Fc gamma receptors.Current research in immunology · 2020Article
- Antigen-Induced Allosteric Changes in a Human IgG1 Fc Increase Low-Affinity Fcγ Receptor Binding.Structure (London, England : 1993) · 2020Article
- A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function.Glycobiology · 2020Review
- Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.ACS synthetic biology · 2019Article
- An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.Nature communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Biologically active conformations of the IgG1 Fc homodimer are maintained by multiple hydrophobic interactions between the protein surface and the N-glycan. The Fc glycan modulates biological effector functions, including antibody-dependent cellular cytotoxicity (ADCC) which is mediated in part through the activatory Fc receptor, FcγRIIIA. Consistent with previous reports, we found that site-directed mutations disrupting the protein-carbohydrate interface (F241A, F243A, V262E, and V264E) increased galactosylation and sialylation of the Fc and, concomitantly, reduced the affinity for FcγRIIIA. We rationalized this effect by crystallographic analysis of the IgG1 Fc F241A mutant, determined here to a resolution of 1.9 Å, which revealed localized destabilization of this glycan-protein interface. Given that sialylation of Fc glycans decreases ADCC, one explanation for the effect of these mutants on FcγRIIIA binding is their increased sialylation. However, a glycan-engineered IgG1 with hypergalactosylated and hypersialylated glycans exhibited unchanged binding affinity to FcγRIIIA. Moreover, when we expressed these mutants as a chemically uniform (Man5GlcNAc2) glycoform, the individual effect of each mutation on FcγRIIIA affinity was preserved. This effect was broadly recapitulated for other Fc receptors (FcγRI, FcγRIIA, FcγRIIB, and FcγRIIIB). These data indicate that destabilization of the glycan-protein interactions, rather than increased galactosylation and sialylation, modifies the Fc conformation(s) relevant for FcγR binding. Engineering of the protein-carbohydrate interface thus provides an independent parameter in the engineering of Fc effector functions and a route to the synthesis of new classes of Fc domain with novel combinations of affinities for activatory and inhibitory Fc receptors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.