Role of glycosylation in nucleating protein folding and stability

Abstract

Glycosylation constitutes one of the most common, ubiquitous and complex forms of post-translational modification. It commences with the synthesis of the protein and plays a significant role in deciding its folded state, oligomerization and thus its function. Recent studies have demonstrated that N-linked glycans help proteins to fold as the stability and folding kinetics are altered with the removal of the glycans from them. Several studies have shown that it alters not only the thermodynamic stability but also the structural features of the folded proteins modulating their interactions and functions. Their inhibition and perturbations have been implicated in diseases from diabetes to degenerative disorders. The intent of this review is to provide insight into the recent advancements in the general understanding on the aspect of glycosylation driven stability of proteins that is imperative to their function and finally their role in health and disease states.

Mass spectrometry for protein sialoglycosylation

“…Negative-ion CID provides abundant glycosidic cleavages and A-type cross-ring cleavages to core structure. 303,305,307,309 A-type ions are useful for determining the position of a sialic acid on α1,3 or α1,6 antennae as well as the presence of a core fucose, although the identification of sialic acid linkages still depends on MS 3 . The cleavage observed in IRMPD is similar to that in CID.…”

“…Glycosylation is the covalent attachment of sugar moieties to a protein by a series of complex enzymatic reactions, constituting one of the most common and diverse co‐translational or post‐translational modifications . These modifications enhance the molecular and functional diversity of the proteome to large degree, providing biological access to vast information space at minimum genetic cost .…”

“…These modifications enhance the molecular and functional diversity of the proteome to large degree, providing biological access to vast information space at minimum genetic cost . Protein glycosylation is involved in various cellular or molecular mechanisms, including protein folding and stability, molecular functional switching, signaling cascades, enzymatic activity, cancer metastasis, cell adhesion, and cell‐cell interactions . A recent review highlights the multifunctional role of glycosylation in organismal diversity, involving structures, modulation, extrinsic recognition, intrinsic recognition, and molecular mimicry .…”

“…A GPI anchor exists in a special form of glycosylation, which links protein C‐terminus with a lipid through a glycan chain . Less common forms include C‐linked glycosylation that occurs on tryptophan or tyrosine residue, and S‐linked glycosylation through a sulphur atom on cysteine or methionine …”

“…forms include C-linked glycosylation that occurs on tryptophan or tyrosine residue, and S-linked glycosylation through a sulphur atom on cysteine or methionine. 3 Most N-linked glycans contain a common core structure consisting of two GlcNAc and three mannose residues. The further modification of the core structure results in three main types of N-glycans, including high mannose, hybrid, and complex glycans.…”