Abstract
Glycosylation is a common and widespread post-translational modification that affects a large majority of proteins. Of these, a small minority, about 20, are specifically modified by the addition of heparan sulfate, a linear polysaccharide from the glycosaminoglycan family. The resulting molecules, heparan sulfate proteoglycans, nevertheless play a fundamental role in most biological functions by interacting with a myriad of proteins. This large functional repertoire stems from the ubiquitous presence of these molecules within the tissue and a tremendous structural variety of the heparan sulfate chains, generated through both biosynthesis and post synthesis mechanisms. The present review focusses on how proteoglycans are “gagosylated” and acquire structural complexity through the concerted action of Golgi-localized biosynthesis enzymes and extracellular modifying enzymes. It examines, in particular, the possibility that these enzymes form complexes of different modes of organization, leading to the synthesis of various oligosaccharide sequences.
Highlights
Protein glycosylation, which takes place in thousands of proteins, is considered as one of the major post-translational modifications in proteins
Chain elongation is a central step in heparan sulfate (HS) biosynthesis and EXT1 and EXT2 activity is regulated through several mechanisms, including changes in gene expression levels, phosphorylation or sulfation of the tetrasaccharide linker region, protein–protein interaction with other HS biosynthesis enzymes and, as mentioned above, localization of the enzymes to different Golgi compartments
This study showed that the heparanase catalytic cleft could accommodate a trisaccharide motif featuring N-S at position -2 and a 6-O-sulfate at position +1
Summary
Protein glycosylation, which takes place in thousands of proteins, is considered as one of the major post-translational modifications in proteins. Tremendous diversity characterizes this family of glycoproteins, due to the variable number and the combination of GAG chains found in each PG and, most importantly, the structural diversity of the GAG chains themselves (see below) Another remarkable feature of PGs is their presence at the cell surface, within the pericellular environment and in the extracellular matrix [2]. (HSPGs)contribute contribute formation of the glycocalyx at cell surface and are present in the extracellular matrix, matrix, where they interact a myriad the cell surface andubiquitously are ubiquitously present in the extracellular where theywith interact with differentofHS bindingHS proteins In doing so, they integrate flow of information inaofmyriad different binding proteins. Deacetylase/N-sulfotransferase enzymes (NDSTs), giving rise to unsubstituted glucosamine (GlcN) This occurs in contiguous stretches ofRemarkably, usually 3–6 disaccharides as S-domains). HS can be further modified by the sulf enzyme, catalyzing specific GlcN 6-O-desulfation [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
