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

被引：90

作者：

Pilecki, Bartosz ^{[1
]}

Holm, Anne T. ^{[1
]}

Schlosser, Anders ^{[1
]}

Moeller, Jesper B. ^{[1
]}

Wohl, Alexander P. ^{[2
]}

Zuk, Alexandra V. ^{[2
]}

Heumueller, Stefanie E. ^{[2
,3
]}

Wallis, Russell ^{[4
,5
]}

Moestrup, Soren K. ^{[1
,6
]}

Sengle, Gerhard ^{[2
,3
]}

Holmskov, Uffe ^{[1
]}

Sorensen, Grith L. ^{[1
]}

机构：

[1] Univ Southern Denmark, Fac Hlth Sci, Inst Mol Med, Dept Canc & Inflammat Res, DK-5000 Odense C, Denmark

[2] Univ Cologne, Fac Med, Ctr Biochem, D-50931 Cologne, Germany

[3] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

[4] Univ Leicester, Dept Infect Immun & Inflammat, Leicester LE1 9HN, Leics, England

[5] Univ Leicester, Dept Mol & Cell Biol, Leicester LE1 9HN, Leics, England

[6] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2016年 / 291卷 / 03期

基金：

英国医学研究理事会;

关键词：

SWISS-MODEL; CRYSTAL-STRUCTURE; CROSS-LINKING; LYSYL-OXIDASE; GLYCOPROTEIN MAGP-36; INNATE IMMUNITY; COACERVATION; EXPRESSION; FICOLIN; DOMAIN;

D O I：

10.1074/jbc.M115.681775

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1103 / 1114

页数：12

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