Domain structure of aggrecan and link protein. Aggrecan binds hyaluronan through its
N-terminal G1 domain in ternary complex with link proteins. The G1 domain and link
proteins are homologous, with an immunoglobulin-like repeat (A) followed by two
proteoglycan tandem repeats (B and B′). In aggrecan, but not in other lecticans, the G1
is followed by a second globular domain (G2), separated from the G1 by an extended
interglobular domain. The G2 domain consists of two proteoglycan tandem repeats (B and
B′). The central, and largest, part of aggrecan is the glycosaminoglycan attachment
region, an extended protein stretch carrying keratan sulfate and chondroitin sulfate
chains. This is followed by the C-terminal G3 domain, which consists of an epidermal
growth factor (EGF) repeat (E1), a calcium-binding EGF repeat (E2), a C-type lectin
domain (L), and a complement regulatory protein repeat (C). Hyaluronan (HA) is shown in
red, aggrecan in blue (core protein) with red glycosaminoglycan chains, link protein in
green. The structural repeat composition of each globular domain of link protein and
aggrecan is shown above and below the two proteins, respectively, as indicated by dashed
lines.