Dataset Information

COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens.

ABSTRACT: COMP (cartilage oligomeric matrix protein) is a member of the thrombospondin family and forms homopentamers as well as mixed heterooligomers with its closely related family member TSP-4. COMP is long known to bind to collagens and to influence collagen fibril formation. Recent work indicates that already intracellular interaction with collagen is important for collagen secretion. However, the exact binding site of COMP on the collagen triple helix has not been described up to now. In this study we have identified a GXKGHR motif on the collagen II helix to bind to COMP, using a recombinantly expressed collagen II peptide library. This binding sequence is conserved throughout evolution and we demonstrate that TSP-4 binds to the same sequence. The identified binding motif overlaps with the recognition sites of many other collagen-binding partners (e.g. PEDF, Heparin) and also spans the lysine residues, which form collagen cross-links. COMP might thereby protect collagen helices from premature modification and cross-linking. Interestingly, this motif is only found in classical fibrillar collagens, although COMP is known to also bind other types. This might indicate that COMP has a unique interface for fibrillar collagens, thus making it an interesting target for the development of antifibrotic drugs.

SUBMITTER: Gebauer JM

PROVIDER: S-EPMC6249252 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens.

Gebauer Jan M JM Köhler Anna A Dietmar Helen H Gompert Monika M Neundorf Ines I Zaucke Frank F Koch Manuel M Baumann Ulrich U

Scientific reports 20181121 1

COMP (cartilage oligomeric matrix protein) is a member of the thrombospondin family and forms homopentamers as well as mixed heterooligomers with its closely related family member TSP-4. COMP is long known to bind to collagens and to influence collagen fibril formation. Recent work indicates that already intracellular interaction with collagen is important for collagen secretion. However, the exact binding site of COMP on the collagen triple helix has not been described up to now. In this study ...[more]

PMID: 30464261

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Project description:ObjectiveRecent studies have associated lower urinary tract symptoms (LUTS) in men with prostatic fibrosis, but a definitive link between collagen deposition and LUTS has yet to be demonstrated. The objective of this study was to evaluate ECM and collagen content within normal glandular prostate tissue and glandular BPH, and to evaluate the association of clinical parameters of LUTS with collagen content.MethodsFibrillar collagen and ECM content was assessed in normal prostate (48 patients) and glandular BPH nodules (24 patients) using Masson's trichrome stain and Picrosirius red stain. Second harmonic generation (SHG) imaging was used to evaluate collagen content. Additional BPH tissues (n = 47) were stained with Picrosirius red and the association between clinical parameters of BPH/LUTS and collagen content was assessed.ResultsECM was similar in normal prostate and BPH (p = 0.44). Total collagen content between normal prostate and glandular BPH was similar (p = 0.27), but a significant increase in thicker collagen bundles was observed in BPH (p = 0.045). Using SHG imaging, collagen content in BPH (mean intensity = 62.52; SEM = 2.74) was significantly higher than in normal prostate (51.77±3.49; p = 0.02). Total collagen content was not associated with treatment with finasteride (p = 0.47) or α-blockers (p = 0.52), pre-TURP AUA symptom index (p = 0.90), prostate-specific antigen (p = 0.86), post-void residual (PVR; p = 0.32), prostate size (p = 0.21), or post-TURP PVR (p = 0.51). Collagen content was not associated with patient age in patients with BPH, however as men aged normal prostatic tissue had a decreased proportion of thick collagen bundles.ConclusionsThe proportion of larger bundles of collagen, but not total collagen, is increased in BPH nodules, suggesting that these large fibers may play a role in BPH/LUTS. Total collagen content is independent of clinical parameters of BPH and LUTS. If fibrosis and overall ECM deposition are associated with BPH/LUTS, this relationship likely exists in regions of the prostate other than glandular hyperplasia.

Dataset Information

COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens.

Publications

COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens.

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