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The proteoglycans aggrecan and versican form networks with fibulin-2 through their lectin domain binding
Author(s): Olin AI, Morgelin M, Sasaki T, Timpl R, Heinegard D, Aspberg A
Source: JOURNAL OF BIOLOGICAL CHEMISTRY    Volume: 276    Issue: 2    Pages: 1253-1261    Published: JAN 12 2001  
Times Cited: 86     References: 48     
Abstract: Aggrecan, versican, neurocan, and brevican are important components of the extracellular matrix in various tissues. Their amino-terminal globular domains bind to hyaluronan, but the function of their carboxyl-terminal globular domains has long remained elusive. A picture is now emerging where the C-type lectin motif of this domain mediates binding to other extracellular matrix proteins. We here demonstrate that aggrecan, versican, and brevican lectin domains bind fibulin-2, whereas neurocan does not. As expected for a C-type lectin, the interactions are calcium-dependent, with K-D values in the nanomolar range as measured by surface plasmon resonance. Solid phase competition assays with previously identified ligands demonstrated that fibulin-2 and tenascin-a bind the same site on the proteoglycan lectin domains. Fibulin-1 has affinity for the common site on versican but may bind to a different site on the aggrecan lectin domain, By using deletion mutants, the interaction sites for aggrecan and versican lectin domains were mapped to epidermal growth factor-like repeats in domain II of fibulin-2. Affinity chromatography and solid phase assays confirmed that also native full-length aggrecan and versican bind the lectin domain ligands, Electron microscopy confirmed the mapping and demonstrated that hyaluronan-aggrecan complexes can be cross-linked by the fibulins.
Document Type: Article
Language: English
Reprint Address: Aspberg, A (reprint author), Univ Lund, Dept Cell & Mol Biol, Sect Connect Tissue Biol, BMC Plan C12, SE-22184 Lund, Sweden
Addresses:
1. Univ Lund, Dept Cell & Mol Biol, Sect Connect Tissue Biol, SE-22184 Lund, Sweden
2. Max Planck Inst Biochem, D-82152 Martinsried, Germany
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Subject Category: Biochemistry & Molecular Biology
IDS Number: 392UL
ISSN: 0021-9258
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