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https://hdl.handle.net/1959.11/20679
Title: | Phosphate modulates receptor sulfotyrosine recognition by the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) | Contributor(s): | Ludeman, Justin P (author); Nazari-Robati, Mahdieh (author); Wilkinson, Brendan (author)![]() |
Publication Date: | 2015 | DOI: | 10.1039/c4ob02262a | Handle Link: | https://hdl.handle.net/1959.11/20679 | Abstract: | Tyrosine sulfation is a widespread post-translational modification that mediates the interactions of secreted and membrane-associated proteins in such varied biological processes as peptide hormone action, adhesion, blood coagulation, complement activation and regulation of leukocyte trafficking. Due to the heterogeneous nature of tyrosine sulfation, detailed biochemical and biophysical studies of tyrosine sulfation rely on homogenous, synthetic sulfopeptides. Here we describe the synthesis of a fluorescent sulfopeptide (FL-R2D) derived from the chemokine receptor CCR2 and the application of FL-R2D in direct and competitive fluorescence anisotropy assays that enable the efficient measurement of binding affinities between sulfopeptides and their binding proteins. Using these assays, we have found that the binding of the chemokine monocyte chemoattractant protein-1 (MCP-1) to sulfated peptides derived from the chemokine receptor CCR2 is highly dependent on the assay buffer. In particular, phosphate buffer at close to physiological concentrations competes with the receptor sulfopeptide by binding to the sulfopeptide binding pocket on the chemokine surface. Thus, physiological phosphate may modulate the receptor binding selectivity of chemokines. | Publication Type: | Journal Article | Grant Details: | ARC/DE130101673 | Source of Publication: | Organic & Biomolecular Chemistry, 13(7), p. 2162-2169 | Publisher: | Royal Society of Chemistry | Place of Publication: | United Kingdom | ISSN: | 1477-0539 1477-0520 |
Fields of Research (FoR) 2008: | 030406 Proteins and Peptides 030404 Cheminformatics and Quantitative Structure-Activity Relationships 030401 Biologically Active Molecules |
Fields of Research (FoR) 2020: | 340401 Biologically active molecules 340407 Proteins and peptides 340404 Cheminformatics and quantitative structure-activity relationships |
Socio-Economic Objective (SEO) 2008: | 929999 Health not elsewhere classified 970103 Expanding Knowledge in the Chemical Sciences 970106 Expanding Knowledge in the Biological Sciences |
Socio-Economic Objective (SEO) 2020: | 280105 Expanding knowledge in the chemical sciences 280102 Expanding knowledge in the biological sciences |
Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article |
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