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http://purl.uniprot.org/citations/26872252http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26872252http://www.w3.org/2000/01/rdf-schema#comment"

Background/aims

The counterbalance of macrophage migration inhibitory factor (MIF) and Gremlin-1 is a useful tool to predict the acuity of coronary artery disease (CAD) and plaque stability. Gremlin1 is an endogenous antagonist of MIF and therefore influences plaque vulnerability. This study was designed to elucidate the mechanistic basis determining the biophysical binding of Gremlin-1 to MIF.

Methods

An in silico model suggested that several charged C-terminal amino acids are crucial in mediating Gremlin-1/MIF-binding. We produced several single amino acid exchange mutants of Gremlin-1 by site-directed mutagenesis. These Gremlin-1 mutants were tested for their ability to reduce MIF effects on monocytes.

Results

We observed that the critical element of the Gremlin-1 molecule for regulating MIF-induced chemotactic activity lies at the C-terminal region. A single amino acid exchange of an arginine to an alanine residue is sufficient to abolish the antagonistic effect of Gremlin-1 on MIF. Therefore, the Gremlin-1 mutant R172A failed to reduce MIF-induced monocyte differentiation into macrophages.

Conclusion

Gremlin-1 C-terminus is essential for antagonizing MIF effects. Our results could offer a novel strategy utilizing Gremlin-1 to target pro-inflammatory effects of MIF in various diseases."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.org/dc/terms/identifier"doi:10.1159/000443035"xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/author"Beck S."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/author"Lang F."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/author"Gawaz M."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/author"Muller I."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/author"Simmet T."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/name"Cell Physiol Biochem"xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/pages"801-808"xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/title"Gremlin-1 C-Terminus Regulates Function of Macrophage Migration Inhibitory Factor (MIF)."xsd:string
http://purl.uniprot.org/citations/26872252http://purl.uniprot.org/core/volume"38"xsd:string
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