Diversity in the processing events at the N‐terminus of type‐V collagen

Moradi-Améli, Mahnaz; Rousseau, Jean-Charles; Kleman, Jean-Philippe; Champliaud, Marie-France; Boutillon, Marguerite‐Marie; Bernillon, Jacques; Wallach, Jean; Rest, Michel van der

doi:10.1111/j.1432-1033.1994.tb18815.x

Cited by 58 publications

(55 citation statements)

References 33 publications

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“…S6). Furthermore, for fibrillar collagen V, the N terminus was shown to be diversely processed in vivo (46). Taken together, these various observations on the C-and N-terminal procollagen cleavage sites suggest greater heterogeneity than was originally thought, which now can be accounted for by the action of meprins.…”

Section: Discussionmentioning

confidence: 53%

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation

Burke

Ding

Singh

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

308

252

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Type I fibrillar collagen is the most abundant protein in the human body, crucial for the formation and strength of bones, skin, and tendon. Proteolytic enzymes are essential for initiation of the assembly of collagen fibrils by cleaving off the propeptides. We report that Mep1a −/− and Mep1b −/− mice revealed lower amounts of mature collagen I compared with WT mice and exhibited significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength. While exploring the mechanism of this phenotype, we found that cleavage of full-length human procollagen I heterotrimers by either meprin α or meprin β led to the generation of mature collagen molecules that spontaneously assembled into collagen fibrils. Thus, meprin α and meprin β are unique in their ability to process and release both C-and N-propeptides from type I procollagen in vitro and in vivo and contribute to the integrity of connective tissue in skin, with consequent implications for inherited connective tissue disorders.proteolysis | Ehlers-Danlos syndrome | proteomics | fibrosis | connective tissue

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Section: Discussionmentioning

confidence: 53%

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation

Burke

Ding

Singh

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

308

252

View full text Add to dashboard Cite

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“…Nevertheless the level of affinity for heparin depends on the chain composition constituting the collagen V molecules. Collagen V can associate into at least three different molecules: [␣1(V)] 2 ␣2(V), found in most tissues; ␣1(V)␣2(V)␣3(V), described only in human placenta; and the homotrimer [␣1(V)] 3 , produced by hamster lung cells and present in some embryonic tissues (11)(12)(13). Indeed, a different apparent affinity for the two heterotrimers for heparin has been described recently by others as a way to purify the two molecular forms from tissues (26).…”

Section: Discussionmentioning

confidence: 99%

“…The predominant molecular form found in most tissues is the heterotrimer [␣1(V)] 2 ␣2(V), whereas the ␣1(V)␣2(V)␣3(V) molecule is only extracted from human placenta (1). The homotrimer [␣1(V)] 3 occurs in cultures of hamster lung cells and was suggested to be present in embryonic tissue (11)(12)(13). It was produced recently as a recombinant molecule (14).…”

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confidence: 99%

Molecular Features of the Collagen V Heparin Binding Site

Delacoux¹,

Fichard

Geourjon

et al. 1998

Journal of Biological Chemistry

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A heparin binding region is known to be present within the triple helical part of the ␣1(V) chain. Here we show that a recombinant ␣1(V) fragment (Ile 824 to Pro 950 ), referred to as HepV, is sufficient for heparin binding at physiological ionic strength. Both native individual ␣1(V) chains and HepV are eluted at identical NaCl concentrations (0.35 M) from a heparin-Sepharose column, and this binding can be inhibited specifically by the addition of free heparin or heparan sulfate. In contrast, a shorter 23-residue synthetic peptide, containing the putative heparin binding site in HepV, fails to bind heparin. Interestingly, HepV promotes cell attachment, and HepV-mediated adhesion is inhibited specifically by heparin or heparan sulfate, indicating that this region might behave as an adhesive binding site. The same site is equally functional on triple helical molecules as shown by heparin-gold labeling. However, the affinities for heparin of each of the collagen V molecular forms tested are different and increase with the number of ␣1(V) chains incorporated in the molecules. Molecular modeling of a sequence encompassing the putative HepV binding sequence region shows that all of the basic residues cluster on one side of the helical face. A highly positively charged ring around the molecule is thus particularly evident for the ␣1(V) homotrimer. This could strengthen its interaction with the anionic heparin molecules. We propose that a single heparin binding site is involved in heparin-related glycosaminoglycanscollagen V interactions, but the different affinities observed likely modulate cell and matrix interactions between collagen V and heparan sulfate proteoglycans in tissues.Collagen V is a fibrillar collagen that plays an important role in fibrillogenesis, and it also acts as an adhesive substrate for a large variety of cells and binds to a number of extracellular components through its major triple helical domain (1). Collagen V interacts with matrix proteoglycans such as the two small proteoglycans decorin and biglycan (2), the proteoglycan form of macrophage colony-stimulating factor (3), the cell surface proteoglycan syndecan-1 (4, 5), and as shown recently, the membrane spanning proteoglycan NG2 (6). Some of these interactions are mediated by the core proteins, but others depend on the glycosaminoglycan chains such as the heparan sulfate chains.Apart from in vitro binding of collagen V to membranespanning proteoglycans, the suggestion that heparan sulfate interacts with collagen V was supported by inhibition experiments showing a reduction of cell attachment to collagen V in the presence of heparin (7). It has been shown already that cell focal adhesion on fibronectin requires the cooperation of both cell transmembrane proteoglycans and integrin receptors (8).Because we have demonstrated already that cell-collagen V interactions involved integrins (9, 10), the binding of membrane-spanning proteoglycans could reinforce cell attachment to collagen V and, in that sense, would be of physiological importance....

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“…Alternatively, the identity of the variable region could influence the rate or extent of proteolytic removal of the ␣1-Npp. The proteolytic processing site is positioned seven amino acids distal to the variable domain at the sequence KAAQA2QEPHIDE (13,14). Recent studies have implied that BMP-1 is responsible for processing as this enzyme cleaves the Npp from ␣1(V) at a homologous sequence (58).…”

Section: Figmentioning

confidence: 99%

“…The PARP (proline-arginine rich protein) domain was originally isolated as a distinct protein from bovine cartilage (11) but was later demonstrated to be a fragment of the N terminus of the ␣2(XI) chain (12). Recently, the proteolytic processing site of the ␣1(XI) chain has been identified (13,14), and since nearly all of the domain is removed by this processing event, both the PARP-like and PARP domains are now termed the amino-propeptides (Npp). The Npp domains are structurally homologous to modules found in seven other collagen chains, as well as the glycoproteins laminin and thrombospondin (15,16).…”

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confidence: 99%

Structural Organization of Distinct Domains within the Non-collagenous N-terminal Region of Collagen Type XI

Gregory¹,

Oxford²,

Chen³

et al. 2000

Journal of Biological Chemistry

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Collagen XI is a heterotrimeric molecule found predominantly in heterotypic cartilage fibrils, where it is involved in the regulation of fibrillogenesis. This function is thought to involve the complex N-terminal domain. The goal of this current study was to examine its structural organization to further elucidate the regulatory mechanism. The amino-propeptide (␣1-Npp) alone or with isoforms of the variable region were recombinantly expressed and purified by affinity and molecular sieve chromatography. Cys-1-Cys-4 and Cys-2-Cys-3 disulfide bonds were detected by liquid chromatographytandem mass spectrometry. This pattern is identical to the homologous ␣2-Npp, indicating that the recombinant proteins were folded correctly. Anomalous elution on molecular sieve chromatography suggested that the variable region was extended, which was confirmed using rotary shadowing; the ␣1-Npp formed a globular "head" and the variable region an extended "tail." Circular dichroism spectra analysis determined that the ␣1-Npp comprised 33% ␤-sheet, whereas the variable region largely comprised non-periodic structure. Taken together, these results imply that the ␣1-Npp cannot be accommodated within the core of the fibril and that the variable region and/or minor helix facilitates its exclusion to the fibril surface. This provides further support for regulation of fibril diameter by steric hindrance or by interactions with other matrix components that affect fibrillogenesis.Collagen XI is a component of fibrils both in cartilage and a wide variety of non-cartilaginous tissues, including brain, muscle, tendon, heart valve, skin, calvaria, and endochondral bone (1, 2). In cartilage it assembles with collagens II and IX to produce an extensive network of thin, heterotypic collagen fibrils (15-25 nm in diameter; Ref. 1) in which the other extracellular matrix components are embedded. The major triple helix of collagen XI is not accessible to antibodies unless the fibrils are disrupted, which led to the model that it is located in the interior of the fibril (1, 3). In non-cartilaginous tissues, collagen XI has been found to co-assemble with chains of the highly homologous type V collagen (4, 5).Collagen XI is a heterotrimeric molecule consisting of ␣1, ␣2, and ␣3 collagen chains (6). The ␣3(XI) chain is an overglycosylated form of the ␣1(II) collagen chain (7), whereas the ␣1(XI) and ␣2(XI) chains are distinct gene products (8). The ␣1(XI) and ␣2(XI) chains contain similar large, N-terminal domains (NTDs), 1 comprising a "PARP" or "PARP-like" domain, a variable region, and a minor triple helix ( Fig. 1a; Refs. 9 and 10). The PARP (proline-arginine rich protein) domain was originally isolated as a distinct protein from bovine cartilage (11) but was later demonstrated to be a fragment of the N terminus of the ␣2(XI) chain (12). Recently, the proteolytic processing site of the ␣1(XI) chain has been identified (13,14), and since nearly all of the domain is removed by this processing event, both the PARP-like and PARP domains are now termed the ...

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Diversity in the processing events at the N‐terminus of type‐V collagen

Cited by 58 publications

References 33 publications

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation

Molecular Features of the Collagen V Heparin Binding Site

Structural Organization of Distinct Domains within the Non-collagenous N-terminal Region of Collagen Type XI

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