Departments of Biological Sciences and Bioengineering, Lehigh University, 111 Research Drive, Bethlehem, PA, 18015, USA.
Published: October 2017
AI Article Synopsis
Article Abstract
Immunoglobulin G1 (IgG1), a subclass of human serum antibodies, is the most widely used scaffold for developing monoclonal antibodies to treat human diseases. The composition of asparagine(N)297-linked glycans can modulate the binding affinity of IgG1 Fc to Fc γ receptors, but it is unclear how the structural modifications of N-glycan termini, which are distal from the binding interface, contribute to the affinity. Through atomistic molecular dynamics simulations of a series of sequentially truncated high-mannose IgG1 Fc glycoforms, we found that the C'E loop and the Cγ2-Cγ3 orientation are highly dynamic, and changes in N-glycan composition alter their conformational ensembles. High-mannose glycoform preferentially samples conformations that are more competent to FcγRIIIa binding, compared to the truncated glycoforms, suggesting a role of IgG1 Fc N-glycan in optimizing the interface with the Fc receptor for efficient binding. The trajectory analyses also reveal that the N-glycan has large amplitude motions and the carbohydrate moiety interconverts between Fc-bound and unbound forms, enabling enzymatic modification of the glycan termini.
Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan. Electronic address:
Background: N-glycosylation is a key post-translational modification critical for protein function and stability. Chitotriosidase-1 (CHIT1), belonging to glycoside hydrolase family 18, is clinically utilized as a biomarker of Gaucher disease. A G102S variant is common in some populations, but the implications of this missense mutation on CHIT1 function and in disease pathology are unknown.
Both endogenous antibodies and a subset of antibody therapeutics engage Fc gamma receptor (FcγR)IIIa/CD16a to stimulate a protective immune response. Increasing the FcγRIIIa/IgG1 interaction improves the immune response and thus represents a strategy to improve therapeutic efficacy. FcγRIIIa is a heavily glycosylated receptor and glycan composition affects antibody-binding affinity.
- Linked glycosylation is a key modification of proteins that impacts lung function by helping proteins fold and facilitating communication between cells, making it crucial for understanding respiratory health.
- The study utilized advanced techniques like MALDI mass spectrometry imaging and co-detection by indexing to identify specific glycan structures in various lung regions, showing their unique locations around different cell types.
- Results indicated that certain glycan types are concentrated around specific cells and areas in the lungs, hinting that these glycan structures may have distinct roles in cellular function and responses, which could inform future lung research.
While tissue amino acid compositions reflect that of the dietary protein source, and the liver orchestrates amino acid metabolism. In this study, we investigated the muscle amino acid profiles in ordinary and crisp grass carp. The 22 amino acids were measured, and seventeen showed significant concentration differences.
Genos Glycoscience Research Laboratory, Zagreb, Croatia; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. Electronic address:
As the global population ages at an unprecedented rate, the prevalence of age-related diseases is increasing, making inflammaging - a phenomenon characterized by a chronic, low-grade inflammatory state that follows aging - a significant concern. Understanding the mechanisms of inflammaging and its impact on health is critical for developing strategies to improve the quality of life and manage health in the aging population. Despite their crucial roles in various biological processes, including immune response modulation, N-glycans, oligosaccharides covalently attached to many proteins, are often overlooked in clinical and research studies.
