Abstract
Chemokines are members of the superfamily of cytokines involved in: (i) cell migration to sites of infection; or (ii) cellular stress during an immune response. Human CXCL14/BRAK is a monocyte-selective chemokine expressed in all normal tissues, but is also involved in the development of several cancers. We describe the expression, structural characterization and biological activity of an N-terminal truncated mutant of CXCL14, ΔCXCL14, where the first eleven residues and the two disulphide bridges were removed. We designed this species in order to analyse the biological importance of the disulphide bonds and the flexible N terminus of CXCL14 for its protein folding, stability and function. The mutant ΔCXCL14 is biologically active, as suggested by the in vitro assays with migration of pancreatic cancer cells, but also its structure is not well-fixed, as suggested by fluorescence, CD and NMR. We conclude that the disulphide bridges are important in maintaining the structure of this chemokine, but they are not necessary for the biological activity of CXCL14 species.
Keywords: Binding, circular dichroism, fluorescence, folding, NMR, structure, stability.
Protein & Peptide Letters
Title:An N-terminally Truncated Mutant of Human Chemokine CXCL14 has Biological Activity
Volume: 20 Issue: 8
Author(s): Jose L. Neira, María J. Sandí, Julio Bacarizo, Cendrine Archange, Ana Camara- Artigas and Juan L. Iovanna
Affiliation:
Keywords: Binding, circular dichroism, fluorescence, folding, NMR, structure, stability.
Abstract: Chemokines are members of the superfamily of cytokines involved in: (i) cell migration to sites of infection; or (ii) cellular stress during an immune response. Human CXCL14/BRAK is a monocyte-selective chemokine expressed in all normal tissues, but is also involved in the development of several cancers. We describe the expression, structural characterization and biological activity of an N-terminal truncated mutant of CXCL14, ΔCXCL14, where the first eleven residues and the two disulphide bridges were removed. We designed this species in order to analyse the biological importance of the disulphide bonds and the flexible N terminus of CXCL14 for its protein folding, stability and function. The mutant ΔCXCL14 is biologically active, as suggested by the in vitro assays with migration of pancreatic cancer cells, but also its structure is not well-fixed, as suggested by fluorescence, CD and NMR. We conclude that the disulphide bridges are important in maintaining the structure of this chemokine, but they are not necessary for the biological activity of CXCL14 species.
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Cite this article as:
Neira L. Jose, Sandí J. María, Bacarizo Julio, Archange Cendrine, Artigas Camara- Ana and Iovanna L. Juan, An N-terminally Truncated Mutant of Human Chemokine CXCL14 has Biological Activity, Protein & Peptide Letters 2013; 20 (8) . https://dx.doi.org/10.2174/09298665113209990040
DOI https://dx.doi.org/10.2174/09298665113209990040 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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