Aggrecan and Versican

 Aggrecan, whose molecular mass is about 2500 kDa, is a typical large keratan sulfate/chondroitin sulfate proteoglycan in cartilagenous tissue. Its distribution pattern is relatively restricted to several tissues including brain, aorta and tendon, in addition to cartilage. The core protein of 210-250 kDa binds hyaluronic acid and forms supramolecular complex together with link protein. Aggrecan provides a strongly hydrated space filling gel due to the large number (more than 100) of polyanionic glycosaminoglycan chains covalently attached to the protein core, and contributes to the physical strength of cartilagenous tissue.

PG-M/versican is a large chondroitin sulfate proteoglycan with an apparent molecular mass of >1000 kDa, and is widely expressed in many tissues. It is substituted with 12-16 chondroitin sulfate chains, much fewer compared with aggrecan, and with a number of N- and O-linked oligosaccharides. Its core protein of approximately 500 kDa binds to hyaluronic acid as does aggrecan.

The two core proteins have structural similarities. The multi-domain structure of their core proteins includes a hyaluronic acid-binding region containing link protein module(s) near the amino terminus, a glycosaminoglycan-attachment domain containing a number of serine-glycine repeats in the middle portion, and a selectin-like domain containing one or two EGF-like repeats, a C-type lectin-like module, and a complement regulatory protein-like module near the carboxyl terminus, as shown in the figure. Both proteoglycans actually bind to hyaluronic acid by their hyaluronic acid-binding region and to various oligosaccharides containing galactose and fucose by the selectin-like domain in a Ca++ dependent manner. Interestingly, the two exons which code glycosaminoglycan-attachment domain of PG-M/versican are alternatively spliced, which yields four different transcripts varying in length of glycosaminoglycan-attachment domain and in the number of glycosaminoglycan chains. Together with neurocan and brevican, both of which are found in brain, they form the aggrecan family (also known as the lectican family or hyalectan family). The structural similarities of these proteoglycans belonging to the aggrecan family suggest their involvement in interactions between the amino terminus and hyaluronic acid in the extracellular matrix or on the cell surface, and between their carboxyl terminus and oligosaccharides in the extracellular matrix or on the cell surface. They form a highly organized extracellular network and present chondroitin sulfate chains of particular length, number and degree of sulfation into the matrix.

Figure Legend
A structural model of aggrecan and PG-M/versican.
The schematic representation below each model shows the organization of peptide domains in aggrecan and PG-M/versican. HABR: hyaluronic acid-binding region; GAG: glycosaminoglycan-attachment domain; EGF: epidermal growth factor-like repeat; LEC: C-type lectin-like module; C: complement regulatory protein-like module.
Toshikazu Yada (Aichi Medical University, Institute for Molecular Science of Medicine)
References(1) Wight, T N, Heinegard, D K, Hascall, V C: Proteoglycans: structure and function. In Hay, E D, ed, Cell Biology of Extracellular Matrix, 2nd edn, Prenum Press, NY, pp.45-78, 1991
(2) Iozzo, RV, Murdoch, A D: Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity and function. FASEB J. 10, 598-614, 1996
Mar.15, 1998

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