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Review
. 2021 Aug 6:9:693563.
doi: 10.3389/fcell.2021.693563. eCollection 2021.

Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools

Bin Zhang  1 , Lianli Chi  1
Affiliations
Review

Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools

Bin Zhang et al. Front Cell Dev Biol. .

Abstract

Chondroitin sulfate (CS) and dermatan sulfate (DS) are linear anionic polysaccharides that are widely present on the cell surface and in the cell matrix and connective tissue. CS and DS chains are usually attached to core proteins and are present in the form of proteoglycans (PGs). They not only are important structural substances but also bind to a variety of cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillary glycoproteins to execute series of important biological functions. CS and DS exhibit variable sulfation patterns and different sequence arrangements, and their molecular weights also vary within a large range, increasing the structural complexity and diversity of CS/DS. The structure-function relationship of CS/DS PGs directly and indirectly involves them in a variety of physiological and pathological processes. Accumulating evidence suggests that CS/DS serves as an important cofactor for many cell behaviors. Understanding the molecular basis of these interactions helps to elucidate the occurrence and development of various diseases and the development of new therapeutic approaches. The present article reviews the physiological and pathological processes in which CS and DS participate through their interactions with different proteins. Moreover, classic and emerging glycosaminoglycan (GAG)-protein interaction analysis tools and their applications in CS/DS-protein characterization are also discussed.

Keywords: analytical methods; chondroitin sulfate; dermatan sulfate; human disease; interaction; protein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The typical disaccharide units present in the backbone of the CS/DS chain. The major types of disaccharide units and sulfate group substitution positions that frequently exist in the CS/DS chains of different classifications are given.
FIGURE 2
FIGURE 2
Complex of CCL5 dimer and CS444. In the cartoon and surface hybrid model, the CS combined area is displayed in red. In the enlarged image, other non-covalent interactions are shown. The yellow dashed line represents hydrogen bonds, the green dashed line represents ionic bonds, and the blue dashed line represents ring-stacking interactions. The figure was prepared using the PDB file originally reported in the reference (Deshauer et al., 2015).
FIGURE 3
FIGURE 3
Major diseases that are related to interactions between CS/DS and proteins.
FIGURE 4
FIGURE 4
Tools for analyzing CS/DS-protein interactions. Affinity chromatography is usually used to isolate binding molecules or fragments. GMSA and microarrays are used to screen the CS/DS or proteins that bind to each other. ITC, SPR, BLI, and QCM can measure the binding strength between CS/DS and proteins. MS and NMR are applied to characterize the structure/sequence of binding motifs. Computational approaches are powerful for simulating the binding postures of these two types of biomolecules.
See this image and copyright information in PMC

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