Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • Our data show a site specific interaction of DDR with

    2020-10-17

    Our data show a site-specific interaction of DDR2 with collagen II. This indicates that the DDRs recognise a particular sequence within collagen and not simply the collagenous triple helix per se. This common tertiary structure of all collagens is formed by three α chains, each with a repeating G-X-Y sequence, in which X and Y are frequently the amino acids proline (P) and hydroxyproline (O), respectively. The structure of a collagen triple helix, however is not uniform and, as suggested previously, site-specific interactions in which fibrillar collagens participate point towards subtle conformational and physicochemical differences between various collagen regions. We demonstrated previously that in collagen II and perhaps in other fibrillar collagens, these structural differences are manifested by differences in thermostabilities of specific D-domains. Cellular interactions with collagens are mediated, to a large part, by cell-surface receptors of the integrin family, which recognise discrete amino rat 4 sequences in triple-helical collagen. An important integrin-binding sequence is GFOGER,22, 23 which is present in a number of different collagens. Two related sequences, GLOGER and GASGER, are also recognised by integrins.23, 24 Another type of receptor for native collagen, the platelet-specific glycoprotein VI (GPVI), is highly specific for the tripeptide G-P-O. Thus, none of the three classes of native collagen receptors discussed here recognises simply the triple-helical conformation. The major collagen-binding integrins α1β1 and α2β1 exhibit multiple recognition sites in collagen I.24, 26 In native collagen II, no specific integrin-binding site has so far been localised, and our previous results with D domain-deleted collagen II imply that the integrin-binding sites are distributed evenly on the collagen II triple helix, as there was no reduction of integrin-dependent attachment of chondrocytes to any of the D domain-deleted collagen II variants compared to full-length collagen II. In contrast to cell attachment, integrin-mediated cell spreading and motility required the collagen II D4 period (amino acid residues 704–938). Similar to integrins, the platelet collagen receptor GPVI is expected to have multiple binding sites on the collagen triple helix due to the frequency of occurrence of the G-P-O tripeptide in collagens. In collagen I, the G-P-O sequence accounts for ∼12% of the primary sequence. In contrast to the situation with integrins and GPVI, our results suggest that DDR2 has a single high-affinity binding site on collagen II, revealing great specificity in the DDR-collagen interaction. A previous study attempted to locate the DDR2 binding site(s) on collagen I by atomic force microscopy and rotary shadowing electron microscopy. Although mostly single DDR2 complexes were observed binding to single collagen molecules, the binding occurred at various positions along the collagen molecule, and attempts were made to reveal the preferred DDR2 binding sites. In our opinion, however, the heterogeneity of the collagen preparation (variation in length from 30nm to 300nm) and lack of polarity preclude any meaningful conclusions about the locations of the DDR2-collagen I interaction. In addition to its interaction with cells, the triple-helical domain of fibrillar collagens interacts specifically with a number of extracellular components and growth and differentiation factors. Some of these interactions have been mapped to defined locations on the collagen triple helix. For example, the leucine-rich proteoglycan decorin was found to bind to a single site near the C terminus of collagen I. These results were, however, disputed in a later study that found multiple binding sites. On collagen I, single binding sites were also found for fibronectin31, 32 and phosphoryn. On the other hand, cartilage oligomeric matrix protein has four binding sites, in equivalent positions, on collagens I and II. Cartilage oligomeric protein is one of very few proteins for which a binding site(s) have been mapped on collagen II. Our previous work has shown that bone morphogenetic protein 2 interacts site-specifically with the D4 period of collagen II.