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

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Citation

Pilecki B, Holm AT, Schlosser A, Moeller JB, Wohl AP, Zuk AV, Heumuller SE, Wallis R, Moestrup SK, Sengle G, Holmskov U, Sorensen GL

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

J Biol Chem. 2016 Jan 15;291(3):1103-14. doi: 10.1074/jbc.M115.681775. Epub 2015 Nov 24.

PubMed ID
26601954 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Protein-lysine 6-oxidaseP28300Details
Fibrillin-2P35556Details