title: The N-terminal domain of CCL21 reconstitutes high affinity binding, G protein activation, and chemotactic activity, to the C-terminal domain of CCL19.
abstract: CC chemokine receptor 7 (CCR7), which regulates the trafficking of leucocytes to the secondary lymphoid organs, has two endogenous chemokine ligands: CCL19 and CCL21. Although both ligands possess similar affinities for the receptor and similar abilities to promote G protein activation and chemotaxis, they share only 25% sequence identity. Here, we show that substituting N-terminal six amino acids of CCL21 (SDGGAQ) for the corresponding N-terminal domain of CCL19 (GTNDAE) results in a chimeric chemokine that exhibits high affinity binding and G protein activation of CCR7. These data demonstrate that despite dissimilar sequences, the amino terminal hexapeptide of these two chemokines is capable of performing similar roles resulting in receptor activation.
authors.affiliation: Department of Endocrinology, Neurocrine Biosciences, San Diego, CA 92130, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ott
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Lio
authors.forename: Dennis
authors.initials: D
authors.lastname: Olshefski
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Liu
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ling
authors.forename: R Scott
authors.initials: RS
authors.lastname: Struthers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D010446:Peptide Fragments; D019204:GTP-Binding Proteins