Universität zu Köln

Pilecki, Bartosz ORCID: 0000-0001-8636-2245, Holm, Anne T., Schlosser, Anders, Moeller, Jesper B., Wohl, Alexander P., Zuk, Alexandra V., Heumueller, Stefanie E., Wallis, Russell ORCID: 0000-0002-8705-5295, Moestrup, Soren K., Sengle, Gerhard, Holmskov, Uffe ORCID: 0000-0002-2391-9445 and Sorensen, Grith L. (2016). Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin-and Fibrillin-binding Protein Involved in Elastic Fiber Formation. J. Biol. Chem., 291 (3). S. 1103 - 1115. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

MFAP4 (microfibrillar-associated protein 4) is an extracellular glycoprotein found in elastic fibers without a clearly defined role in elastic fiber assembly. In the present study, we characterized molecular interactions between MFAP4 and elastic fiber components. We established that MFAP4 primarily assembles into trimeric and hexameric structures of homodimers. Binding analysis revealed that MFAP4 specifically binds tropoelastin and fibrillin-1 and -2, as well as the elastin cross-linking amino acid desmosine, and that it co-localizes with fibrillin-1-positive fibers in vivo. Site-directed mutagenesis disclosed residues Phe(241) and Ser(203) in MFAP4 as being crucial for type I collagen, elastin, and tropoelastin binding. Furthermore, we found that MFAP4 actively promotes tropoelastin self-assembly. In conclusion, our data identify MFAP4 as a new ligand of microfibrils and tropoelastin involved in proper elastic fiber organization.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pilecki, Bartosz UNSPECIFIED orcid.org/0000-0001-8636-2245 UNSPECIFIED Holm, Anne T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlosser, Anders UNSPECIFIED UNSPECIFIED UNSPECIFIED Moeller, Jesper B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohl, Alexander P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuk, Alexandra V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heumueller, Stefanie E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wallis, Russell UNSPECIFIED orcid.org/0000-0002-8705-5295 UNSPECIFIED Moestrup, Soren K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sengle, Gerhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Holmskov, Uffe UNSPECIFIED orcid.org/0000-0002-2391-9445 UNSPECIFIED Sorensen, Grith L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-287207
DOI:	10.1074/jbc.M115.681775
Journal or Publication Title:	J. Biol. Chem.
Volume:	291
Number:	3
Page Range:	S. 1103 - 1115
Date:	2016
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SWISS-MODEL; CRYSTAL-STRUCTURE; CROSS-LINKING; LYSYL-OXIDASE; GLYCOPROTEIN MAGP-36; INNATE IMMUNITY; COACERVATION; EXPRESSION; FICOLIN; DOMAIN Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28720