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| 2. |
- Lundell, Anna, et al.
(författare)
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Structural basis for interactions between tenascins and lectican C-type lectin domains: evidence for a crosslinking role for tenascins.
- 2004
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Ingår i: Structure. - : Elsevier BV. - 0969-2126. ; 12:8, s. 1495-1506
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Tidskriftsartikel (refereegranskat)abstract
- The C-terminal G3 domains of lecticans mediate crosslinking to diverse extracellular matrix (ECM) proteins during ECM assembly, through their C-type lectin (CLD) subdomains. The structure of the rat aggrecan CLD in a Ca(2+)-dependent complex with fibronectin type III repeats 3-5 of rat tenascin-R provides detailed support for such crosslinking. The CLD loops bind Ca2+ like other CLDs, but no carbohydrate binding is observed or possible. This is thus the first example of a direct Ca(2+)-dependent protein-protein interaction of a CLD. Surprisingly, tenascin-R does not coordinate the Ca2+ ions directly. Electron microscopy confirms that full-length tenascin-R and tenascin-C crosslink hyaluronan-aggrecan complexes. The results are significant for the binding of all lectican CLDs to tenascin-R and tenascin-C. Comparison of the protein interaction surface with that of P-selectin in complex with the PGSL-1 peptide suggests that direct protein-protein interactions of Ca(2+)-binding CLDs may be more widespread than previously appreciated.
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| 3. |
- Olin, Anders, et al.
(författare)
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The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding
- 2001
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:2, s. 1253-1261
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
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| 5. |
- Bengtsson, E, et al.
(författare)
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The amino-terminal part of PRELP binds to heparin and heparan sulfate
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:52, s. 40695-40702
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Tidskriftsartikel (refereegranskat)abstract
- PRELP (proline, arginine-rich end leucine-rich repeat protein) is an extracellular matrix leucine-rich repeat protein. The amino-terminal region of PRELP differs from that of other leucine-rich repeat proteins in containing a high number of proline and arginine residues. The clustered proline and basic residues are conserved in rat, bovine, and human PRELP. Although the function of PRELP is not yet known, the clustered arginine residues suggest a heparan sulfate/heparin-binding capacity. We show here that PRELP indeed binds heparin and heparan sulfate. Truncated PRELP without the amino-terminal region does not bind heparin. The dissociation constant for the interaction of PRELP with heparin was determined by an in solution binding assay and by surface plasmon resonance analysis to be in the range of 10-30 nm. A 6-mer heparin oligosaccharide was the smallest size showing binding to PRELP. The binding increased with increasing length up to an 18-mer and depended on the degree of sulfation of heparin as well as heparan sulfate. Sulfate groups at all positions were shown to be of importance for the binding. Fibroblasts bind PRELP, and this interaction is inhibited with heparin, suggesting a function for PRELP as a linker between the matrix and cell surface proteoglycans.
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| 6. |
- Bengtsson, Eva, et al.
(författare)
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The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement anchor.
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:17, s. 15061-15068
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Tidskriftsartikel (refereegranskat)abstract
- PRELP is a heparin-binding leucine-rich repeat protein in connective tissue extracellular matrix. In search of natural ligands and biological functions of this molecule, we found that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan. Also recombinant perlecan domains I and V carrying heparan sulfate bound PRELP, whereas other domains without glycosaminoglycan substitution did not. Heparin, but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free recombinant perlecan domain V and mutated domain I did not bind PRELP. The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nM as determined by surface plasmon resonance. As expected, truncated PRELP, without the heparin-binding domain, did not bind perlecan. Confocal immunohistochemistry showed that PRELP outlines basement membranes with a location adjacent to perlecan. We also found that PRELP binds collagen type I and type II through its leucine-rich repeat domain. Electron microscopy visualized a complex with PRELP binding simultaneously to the triple helical region of procollagen I and the heparan sulfate chains of perlecan. Based on the location of PRELP and its interaction with perlecan heparan sulfate chains and collagen, we propose a function of PRELP as a molecule anchoring basement membranes to the underlying connective tissue.
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| 7. |
- Heinegård, Dick, et al.
(författare)
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Glycosylated matrix protein
- 2002
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Ingår i: Connective tissue and its heritable disorders: molecular, genetic, and medical aspects, 2nd edition. - Hoboken, NJ, USA : John Wiley & Sons, Inc.. - 9780471251859 ; , s. 271-291
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Connective tissues have many features in common, including resisting and dissipating mechanical load and providing shape, as well as acting to provide barriers regulating water flow and diffusibility of macromolecules. In this chapter we have chosen to focus on cartilage and bone, covering many aspects of connective tissues. We give special focus to the noncollagenous proteins in their matrices.
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| 8. |
- Heinegård, Dick, et al.
(författare)
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Glycosylated Matrix Proteins
- 2002
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Ingår i: Connective Tissue and Its Heritable Disorders: Molecular, Genetic and Medical Aspects. - Hoboken, NJ, USA : John Wiley & Sons, Inc.. - 9780471251859 - 9780471221920 ; , s. 271-291
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Connective tissues have many features in common, including resisting and dissipating mechanical load and providing shape, as well as acting to provide barriers regulating water flow and diffusibility of macromolecules. In this chapter we have chosen to focus on cartilage and bone, covering many aspects of connective tissues. We give special focus to the noncollagenous proteins in their matrices.
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| 9. |
- Isogai, Z, et al.
(författare)
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Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:6, s. 4565-4572
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Tidskriftsartikel (refereegranskat)abstract
- Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
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| 10. |
- Lorenzo, Pilar, et al.
(författare)
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Identification and characterization of asporin. a novel member of the leucine-rich repeat protein family closely related to decorin and biglycan
- 2001
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:15, s. 12201-12211
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Tidskriftsartikel (refereegranskat)abstract
- Asporin, a novel member of the leucine-rich repeat family of proteins, was partially purified from human articular cartilage and meniscus. Cloning of human and mouse asporin cDNAs revealed that the protein is closely related to decorin and biglycan. It contains a putative propeptide, 4 amino-terminal cysteines, 10 leucine-rich repeats, and 2 C-terminal cysteines. In contrast to decorin and biglycan, asporin is not a proteoglycan. Instead, asporin contains a unique stretch of aspartic acid residues in its amino-terminal region. A polymorphism was identified in that the number of consecutive aspartate residues varied from 11 to 15. The 8 exons of the human asporin gene span 26 kilobases on chromosome 9q31.1-32, and the putative promoter region lacks TATA consensus sequences. The asporin mRNA is expressed in a variety of human tissues with higher levels in osteoarthritic articular cartilage, aorta, uterus, heart, and liver. The deduced amino acid sequence of asporin was confirmed by mass spectrometry of the isolated protein resulting in 84% sequence coverage. The protein contains an N-glycosylation site at Asn(281) with a heterogeneous oligosaccharide structure and a potential O-glycosylation site at Ser(54). The name asporin reflects the aspartate-rich amino terminus and the overall similarity to decorin.
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