| 1. |
- Aspberg, Anders, et al.
(författare)
-
Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican
- 1999
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:29, s. 20444-20449
-
Tidskriftsartikel (refereegranskat)abstract
- The aggregating proteoglycans (aggrecan, versican, neurocan, and brevican) are important components of many extracellular matrices. Their N-terminal globular domain binds to hyaluronan, but the function of their C-terminal region 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 acid 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), and also expressed in developing cartilage and bone. It is thus likely to interact with these proteoglycans in vivo. Surface plasmon resonance measurements confirmed that aggrecan and versican lectin domains bind fibulin-1, whereas brevican and neurocan do not. As expected for a C-type lectin, the interactions with fibulin-1 are Ca2+-dependent, with KD values in the low nanomolar range. Using various deletion mutants, the binding site for aggrecan and versican lectin domains was mapped to the epidermal growth factor-like repeats in domain II of fibulin-1. No difference in affinity was found for deglycosylated fibulin-1, indicating that the proteoglycan C-type lectin domains bind to the protein part of fibulin-1.
|
|
| 2. |
- Aspberg, Anders, et al.
(författare)
-
The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety
- 1997
-
Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 94:19, s. 10116-10121
-
Tidskriftsartikel (refereegranskat)abstract
- The lecticans are a family of chondroitin sulfate proteoglycans including aggrecan, versican, neurocan, and brevican. The C-terminal globular domains of lecticans are structurally related to selectins, consisting of a C-type lectin domain flanked by epidermal growth factor and complement regulatory protein domains. The C-type lectin domain of versican has been shown to bind tenascin-R, an extracellular matrix protein specifically expressed in the nervous system, and the interaction was presumed to be mediated by a carbohydrate-protein interaction. In this paper, we show that the C-type lectin domain of brevican, another lectican that is specifically expressed in the nervous system, also binds tenascin-R. Surprisingly, this interaction is mediated by a protein-protein interaction through the fibronectin type III domains 3-5 of tenascin-R, independent of any carbohydrates or sulfated amino acids. The lectin domains of versican and other lecticans also bind the same domain of tenascin-R by protein-protein interactions. Surface plasmon resonance analysis revealed that brevican lectin has at least a 10-fold higher affinity than the other lectican lectins. Tenascin-R is coprecipitated with brevican from adult rat brain extracts, suggesting that tenascin-R and brevican form complexes in vivo. These results demonstrate that the C-type lectin domain can interact with fibronectin type III domains through protein-protein interactions, and suggest that brevican is a physiological tenascin-R ligand in the adult brain.
|
|
| 3. |
- Aspberg, Anders, et al.
(författare)
-
The versican C-type lectin domain recognizes the adhesion protein tenascin-R
- 1995
-
Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 92:23, s. 10590-10594
-
Tidskriftsartikel (refereegranskat)abstract
- The core proteins of large chondroitin sulfate proteoglycans contain a C-type lectin domain. The lectin domain of one of these proteoglycans, versican, was expressed as a recombinant 15-kDa protein and shown to bind to insolubilized fucose and GlcNAc. The lectin domain showed strong binding in a gel blotting assay to a glycoprotein doublet in rat brain extracts. The binding was calcium dependent and abolished by chemical deglycosylation treatment of the ligand glycoprotein. The versican-binding glycoprotein was identified as the cell adhesion protein tenascin-R, and versican and tenascin-R were both found to be localized in the granular layer of rat cerebellum. These results show that the versican lectin domain is a binding domain with a highly targeted specificity. It may allow versican to assemble complexes containing proteoglycan, an adhesion protein, and hyaluronan.
|
|
