Universität zu Köln

Gebauer, Jan M., Koehler, Anna, Dietmar, Helen, Gompert, Monika, Neundorf, Ines ORCID: 0000-0001-6450-3991, Zaucke, Frank ORCID: 0000-0002-7680-9354, Koch, Manuel and Baumann, Ulrich (2018). COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gebauer, Jan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehler, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietmar, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gompert, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Zaucke, Frank UNSPECIFIED orcid.org/0000-0002-7680-9354 UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-165500
DOI:	10.1038/s41598-018-35447-8
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OLIGOMERIC MATRIX PROTEIN; CRYSTAL-STRUCTURE; SIGNATURE DOMAIN; I COLLAGEN; CARTILAGE; BINDING; THROMBOSPONDIN-4; CALCIUM; PARTNERS; HSP47 Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16550