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Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation

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DOI

  • Bartosz Pilecki, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Anne T Holm, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Anders Schlosser, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Jesper B Moeller, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Alexander P Wohl, University of Gothenburg
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  • Alexandra V Zuk, University of Gothenburg
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  • Stefanie E Heumüller, the Center for Biochemistry, Faculty of Medicine and the Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
  • ,
  • Russell Wallis, the Department of Infection, Immunity and Inflammation, and Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, United Kingdom, and.
  • ,
  • Soren K Moestrup
  • Gerhard Sengle, the Center for Biochemistry, Faculty of Medicine and the Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
  • ,
  • Uffe Holmskov, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
  • ,
  • Grith L Sorensen, From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark, glsorensen@health.sdu.dk.

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.

Original languageEnglish
JournalThe Journal of biological chemistry
Volume291
Issue3
Pages (from-to)1103-14
Number of pages12
DOIs
Publication statusPublished - 15 Jan 2016
Externally publishedYes

    Research areas

  • Amino Acid Substitution, Animals, Carrier Proteins, Desmosine, Elastic Tissue, Extracellular Matrix Proteins, Fibrillin-1, Fibrillins, Glycoproteins, Humans, Ligands, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Microfibrils, Microfilament Proteins, Models, Molecular, Mutation, Peptide Fragments, Protein Interaction Domains and Motifs, Protein Isoforms, Protein Multimerization, Protein Transport, Recombinant Proteins, Tropoelastin, Journal Article, Research Support, Non-U.S. Gov't

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