Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation.
J Biol Chem
; 291(3): 1103-14, 2016 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-26601954
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.
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MEDLINE
Assunto principal:
Glicoproteínas
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Proteínas de Transporte
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Modelos Moleculares
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Proteínas da Matriz Extracelular
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Tropoelastina
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Microfibrilas
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Desmosina
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Tecido Elástico
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Proteínas dos Microfilamentos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article