Where is IgG glycosylated?
Each IgG molecule carries two glycans covalently attached to conserved glycosylation sites at Asn–297 of the constant heavy 2 (CH2) domain on each of its heavy chains (Fig. 1). They are positioned within the cavity formed by the polypeptide chains of the two CH2 domains and are generally partially processed [2], [3].
What is Fc glycosylation?
Glycosylation of IgG Fc domains is a central mechanism in the diversification of antibody function. Modifications to the core Fc glycan impact antibody function by shifting the balance of Type I and Type II Fc gamma receptors (FcγR) that will be engaged by immune complexes.
Does IgG bind to Fc?
The IgG Fc contains distinct Fc receptor (FcR) binding sites: the leukocyte receptors Fc gamma RI and Fc gamma RIIa bind to a region in the Fc distinct from that recognized by neonatal FcR and protein A. J Immunol.
What is Fc in IgG?
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune system.
Are antibodies glycosylated?
Antibody glycosylation is a common post-translational modification and has a critical role in antibody effector function. The use of glycoengineering to produce antibodies with specific glycoforms may be required to achieve the desired therapeutic efficacy.
Are all antibodies glycosylated?
Antibody Fc glycosylation. Beyond isotype selection, every antibody Fc is also post-translationally modified via the addition of N-glycans at specific asparagine residues on the antibody heavy chain (Arnold et al. 2007).
What is IgG made of?
IgG antibodies are large globular proteins with a molecular weight of about 150 kDa made of four peptide chains. It contains two identical γ (gamma) heavy chains of about 50 kDa and two identical light chains of about 25 kDa, thus a tetrameric quaternary structure.
What is the function of IgG?
IgG antibody structure and function IgG protects against bacteria, viruses, neutralises bacterial toxins, triggers complement protein systems and binds antigens to enhance the effectiveness of phagocytosis.
What does high IgG antibodies mean?
High levels of IgG may mean a long-term (chronic) infection, such as HIV, is present. Levels of IgG also get higher in IgG multiple myeloma, long-term hepatitis, and multiple sclerosis (MS).
What is the purpose of glycosylation?
Glycosylation is an important and highly regulated mechanism of secondary protein processing within cells. It plays a critical role in determining protein structure, function and stability. Structurally, glycosylation is known to affect the three dimensional configuration of proteins.
Where does the glycosylation of IgG take place?
All four subclasses of human serum IgG contain a single N-glycosylation site in the constant region of their heavy chain, which is occupied by biantennary, largely core-fucosylated and partially truncated oligosaccharides, that may carry a bisecting N-acetylglucosamine and sialic acid residues. IgG …
Where is the N-glycan located in IgG-Fc?
The regions recognizing the antigen and the cellular FcγRs are termed Fab and Fc, respectively. The orange stars indicate the approximate position where the N-glycan is attached to residue Asn297 of the CH2 domain.
Which is an effector of conserved IgG Fc N glycosylation?
Influence of conserved IgG Fc N-glycosylation on effector functions (i.e. ADCC and CDC) and PK is well known and there are several reviews available covering this topic [2], [3].
Where are the interaction sites of IgG Fc?
The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc all …