Unusual glycosylation of proteins: Beyond the universal sequon and other amino acids

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 12; pp. 3096 - 3108
• Main Authors: Dutta, Devawati, Mandal, Chhabinath, Mandal, Chitra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2017
• Subjects: Amino Acid Sequence; Amino acids; Amino Acids - metabolism; asparagine; Biological functions; biomarkers; C-Reactive Protein - metabolism; glycosidic linkages; Glycosylation; Humans; Immunoglobulin G - metabolism; moieties; Motif; N-acetylglucosamine; Non-consensus; Pathological conditions; proline; Protein Processing, Post-Translational; proteins; Proteins - metabolism; serine; threonine; Unusual glycosylation; Non-consensus; Amino acids; Unusual glycosylation; Pathological conditions; Biological functions; Motif
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.08.025

Glycosylation of proteins is the most common, multifaceted co- and post-translational modification responsible for many biological processes and cellular functions. Significant alterations and aberrations of these processes are related to various pathological conditions, and often turn out to be disease biomarkers. Conventional N-glycosylation occurs through the recognition of the consensus sequon, asparagine (Asn)-X-serine (Ser)/threonine (Thr), where X is any amino acid except for proline, with N-acetylglucosamine (GlcNAc) as the first glycosidic linkage. Usually, O-glycosylation adds a glycan to the hydroxyl group of Ser or Thr beginning with N-acetylgalactosamine (GalNAc). Protein glycosylation is further governed by additional diversifications in sequon and structure, which are yet to be fully explored. This review mainly focuses on the occurrence of N-glycosylation in non-consensus motifs, where Ser/Thr at the +2 position is substituted by other amino acids. Additionally, N-glycosylation is also observed in other amide/amine group-containing amino acids. Similarly, O-glycosylation occurs at hydroxyl group-containing amino acids other than serine/threonine. The neighbouring amino acids and local structural features around the potential glycosylation site also play a significant role in determining the extent of glycosylation. All of these phenomena that yield glycosylation at the atypical sites are reported in a variety of biological systems, including different pathological conditions. Therefore, the discovery of more novel sequence patterns for N- and O-glycosylation may help in understanding the functions of complex biological processes and cellular functions. Taken together, all these information provided in this review would be helpful for the biological readers. [Display omitted] •Protein glycosylation is governed by diversifications in sequon highlighting that N-glycosylation motif (Asn-X-Ser/Thr) is not the general rule.•Glycosylation also occurs in non-consensus motifs.•Amino acids other than Asn/Ser/Thr are involved.•Such non-consensus motifs exhibit relevance in many cellular functions.•Therefore, the discovery of more such novel sequons will open up a new arena to understand the various unique mechanism of the glycosylation machinery.•This overview demonstrates that our knowledge is expanding beyond the common rules for glycosylation.