Group I - Proteoglycans
The proteoglycan group of CTLD-containing extracellular matrix
proteins has four members in both human and mouse, which are also known as
lecticans or hyalectans. Neurocan and brevican are expressed in the
central nervous system, aggrecan is found principally in cartilage, and
versican has a wide tissue distribution. The N-terminal region of a
lectican polypeptide consists of an immunoglobulin domain and multiple
link modules. The central region, which is divergent and varies
significantly in length between different lecticans, serves as an
attachment region for glycosaminoglycan chains, primarily chondroitin
sulphate. The C-terminal region consists of a CTLD sandwiched
between one or two epidermal growth factor (EGF)-like domains and a
complement control domain. Brevican is also produced in a truncated,
glycosylphosphatidyl inositol-anchored form.
High molecular weight aggregates are formed by the binding of multiple lectican polypeptides, through link modules, to a molecule of hyaluronan. Lectican aggregates have structural roles in the extracellular matrix. The resilience of cartilage, which cushions joints, is due to the hydrated glycosaminoglycan chains of aggrecan. Furthermore, the glycosaminoglycan chains and globular domains of lecticans can bind cell surface molecules, matrix components, and extracellular signalling molecules through interactions with protein, lipid or carbohydrate. These interactions are modulated by spatial and temporal variations in lectican expression, splicing, proteolysis, and glycosylation, and by other ligands and signalling molecules. As a consequence, lecticans have complex effects on cell communication, adhesion, migration, proliferation, differentiation and apoptosis. The modulation of these events by lecticans is implicated in development, tissue remodelling, and disease, including cancer and arthritis.
The CTLDs in lecticans appear to be of the galactose-binding subtype. The CRD of aggrecan exhibits calcium-dependent binding to galactose and related sugars, but the physiological role of this carbohydrate recognition remains unknown. Lectican CTLDs also participate in protein-protein interactions.
The aggrecan CTLD is shown in red (alpha-helices) and blue (beta-strands). Ca2+ ions are shown in dark blue. Tenascin R is shown in yellow. Protein Data Bank structure ID: 1TDQ.
