title: An N-terminally truncated mutant of human chemokine CXCL14 has biological activity.
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.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche (Alicante), Spain. jlneira@umh.es
authors.forename: José L
authors.initials: JL
authors.lastname: Neira
authors.forename: María J
authors.initials: MJ
authors.lastname: Sandí
authors.forename: Julio
authors.initials: J
authors.lastname: Bacarizo
authors.forename: Cendrine
authors.initials: C
authors.lastname: Archange
authors.forename: Ana
authors.initials: A
authors.lastname: Camara-Artigas
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D019743:Chemokines, CXC / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D050505:Mutant Proteins; D006493:Heparin