Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican

The aggregating proteoglycans (aggrecan, versican, neurocan, and brevican) are important components of many extracellular matrices. Their N-terminal g lobular domain binds to hyaluronan, but the function of their C-terminal re gion containing a C-type lectin domain is less clear. We now report that a 90-kDa protein copurifies with recombinant lectin domains from aggrecan and versican, but not from the brain-specific neurocan and brevican. Amino aci d sequencing of tryptic peptides from this protein identified it as fibulin -1. This extracellular matrix glycoprotein is strongly expressed in tissues where versican is expressed (blood vessels, skin, and developing heart), a nd also expressed in developing cartilage and bone. It is thus likely to in teract with these proteoglycans in vivo. Surface plasmon resonance measurem ents confirmed that aggrecan and versican lectin domains bind fibulin-1, wh ereas brevican and neurocan do not. As expected for a C-type lectin, the in teractions with fibulin-1 are Ca2+-dependent, with K-D values in the low na nomolar range. Using various deletion mutants, the binding site for aggreca n and versican lectin domains was mapped to the epidermal growth factor-lik e repeats in domain II of fibulin-1. No difference in affinity was found fo r deglycosylated fibulin-1, indicating that the proteoglycan C-type lectin domains bind to the protein part of fibulin-1.