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The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding

Olin, Anders LU ; Mörgelin, Matthias LU ; Sasaki, Takako; Timpl, Rupert; Heinegård, Dick LU and Aspberg, Anders LU (2001) In Journal of Biological Chemistry 276(2). p.1253-1261
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... (More)
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-R 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. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
276
issue
2
pages
1253 - 1261
publisher
ASBMB
external identifiers
  • pmid:11038354
  • scopus:0035847046
ISSN
1083-351X
DOI
10.1074/jbc.M006783200
language
English
LU publication?
yes
id
b691ac45-ce3e-4a7f-8be7-cfeb6a82b66e (old id 1122282)
date added to LUP
2008-07-09 09:07:44
date last changed
2018-01-07 06:09:31
@article{b691ac45-ce3e-4a7f-8be7-cfeb6a82b66e,
  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-R 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.},
  author       = {Olin, Anders and Mörgelin, Matthias and Sasaki, Takako and Timpl, Rupert and Heinegård, Dick and Aspberg, Anders},
  issn         = {1083-351X},
  language     = {eng},
  number       = {2},
  pages        = {1253--1261},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding},
  url          = {http://dx.doi.org/10.1074/jbc.M006783200},
  volume       = {276},
  year         = {2001},
}