title: Backbone dynamics of the CC-chemokine eotaxin-2 and comparison among the eotaxin group chemokines.
abstract: The eotaxin group chemokines (eotaxin, eotaxin-2, and eotaxin-3) share only 35-41% sequence identity but are all agonists for the receptor CCR3. Here we present a detailed comparison between the backbone dynamics of these three chemokines. The dynamics of eotaxin-2 were determined from 15N NMR relaxation data and compared to those obtained previously for eotaxin and eotaxin-3. For all three chemokines, the majority of residues in the first two beta-strands and the alpha-helix show highly restricted motions on the subnanosecond time scale but there is dramatically higher flexibility in the N- and C-terminal regions and also substantial mobility for residues in the N-loop region and the third beta-strand. The latter two regions form a groove on the chemokine surface that is the likely binding site for the N-terminal region of the receptor. Taken together, the available data suggest a model in which conformational rearrangements of both the chemokine and the receptor are likely to occur during binding and receptor activation.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405-0001, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Mayer
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stone
mesh_terms: D001665:Binding Sites; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000737:chemistry* / Q000378:metabolism; D004058:Diffusion; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D018583:Pliability; D017433:Protein Structure, Secondary; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000737:chemistry / Q000378:metabolism; D012399:Rotation
chemical_list: C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine