Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity

TL;DR

This review explains how a small number of enzymes and proteins create diverse heparan sulfate structures, which are important for many biological functions.

Contribution

The paper explores how enzyme complexes generate structural diversity in heparan sulfate proteoglycans through biosynthesis and post-synthesis mechanisms.

Findings

Heparan sulfate proteoglycans are modified by a small number of enzymes and core proteins.

Structural diversity arises from both biosynthesis and post-synthesis processes.

Enzyme complexes may organize in different ways to produce varied oligosaccharide sequences.

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.

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