title: Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding.
abstract: Chemokines direct the migration of cells during various immune processes and are involved in many disease states. For example, CCL19 and CCL21, through activation of the CCR7 receptor, recruit dendritic cells and naïve T-cells to the secondary lymphoid organs aiding in balancing immune response and tolerance. However, CCL19 and CCL21 can also direct the metastasis of CCR7 expressing cancers. Chemokine binding to glycosaminoglycans, such as heparin, is as important to chemokine function as receptor activation. CCL21 is unique in that it contains an extended C-terminus not found in other chemokines like CCL19. Deletion of this extended C-terminus reduces CCL21's affinity for heparin and transferring the CCL21 C-terminus to CCL19 enhances heparin binding mainly through non-specific, electrostatic interactions.
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Barmore
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Castex
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Gouletas
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Griffith
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Slater W
authors.initials: SW
authors.lastname: Metz
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Muelder
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Populin
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Sackett
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Schuster
authors.affiliation: Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA; Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: veldkamc@uww.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Veldkamp
mesh_terms: D000595:Amino Acid Sequence; D054415:Chemokine CCL19 / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D006493:Heparin
keywords: CCL19; CCL21; Chemokines; Chimeric protein; Glycosaminoglycans; Heparin