The role of link-protein in the structure of cartilage proteoglycan aggregates

Abstract

Proteoglycan fractions were prepared from pig laryngeal cartilage. The effect of link-protein on the properties of proteoglycan-hyaluronate aggregates was examined by viscometry and analytical ultracentrifugation. Aggregates containing link-protein were more stable than link-free aggregates at neutral pH, at temperatures up to 50 degrees C and in urea (up to 4.0M). Oligosaccharides of hyaluronate were able to displace proteoglycans from link-free aggregates, but not from the link-stabilized aggregates. Both types of aggregate were observed in the ultracentrifuge, but at the concentration investigated (less than 2 mg/ml) the link-free form was partially dissociated and the proportion aggregated varied with the pH and temperature and required more hyaluronate for saturation than did link-stabilized aggregate. The results showed that link-protein greatly strengthened the binding of proteoglycans to hyaluronate and suggest that under physiological conditions it 'locks' proteoglycans on to the hyaluronate chain.

Evidence of a defined spatial arrangement of hyaluronate in the central filament of cartilage proteoglycan aggregates

“…The binding is through a specialized portion of their core protein, the hyaluronate-binding region [6], to a decasaccharide segment of the hyaluronate chain [9]. This interaction is stabilized by the binding of a small glycoprotein, the link protein [6,8], with affinity for both hyaluronate [9,10] and the hyaluronate-binding region of the aggrecan monomer, leading to the formation of a very stable ternary complex [11]. This model has been extended by a combination of electron microscopy [12][13][14] and sequence analysis at the protein [15] and cDNA [16][17][18][19][20] level.…”

Hyaluronan-dependent pericellular matrix☆

“…When excess proteoglycan is added to the coat, the pore size of the pericellular matrix is decreased, with particles 0.3 microns or larger excluded [18]. Link proteins stabilize the interaction between hyaluronic acid and proteoglycans [19][20][21] and have been shown to have a shortening effect on the length of hyaluronan that is similar to the proteoglycan [17]. Others have shown that adding an excess of link proteins can cause fragmentation or disruption of hyaluronan networks [22].…”

Cartilage proteoglycans

“…This protein was given the simple name 'link protein'. 7 The tripartite linkage of aggrecan, link protein and hyaluronan is essentially non-dissociating and non-displaceable under physiological conditions. This interaction represents the primary reason why chaotropic agents are necessary to extract aggrecan from cartilage.…”