TY  - JOUR
A1  - Gebauer, Jan Martin Ulrich
A1  - Köhler, Anna
A1  - Dietmar, Helen
A1  - Gompert, Monika
A1  - Neundorf, Ines
A1  - Zaucke, Frank
A1  - Koch, Manuel
A1  - Baumann, Ulrich
T1  - COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens
T2  - Scientific reports
N2  - 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.
KW  - Molecular medicine
KW  - Proteins
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48494
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-484949
SN  - 2045-2322
N1  - Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 8
IS  - 1, Art. 17187
SP  - 1
EP  - 13
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -