title: Chemokine and chemokine receptor structure and interactions: implications for therapeutic strategies.
abstract: The control of cell migration by chemokines involves interactions with two types of receptors: seven transmembrane chemokine-type G protein-coupled receptors and cell surface or extracellular matrix-associated glycosaminoglycans. Coordinated interaction of chemokines with both types of receptors is required for directional migration of cells in numerous physiological and pathological processes. Accumulated structural information, culminating most recently in the structure of a chemokine receptor in complex with a chemokine, has led to a view where chemokine oligomers bind to glycosaminoglycans through epitopes formed when chemokine subunits come together, while chemokine monomers bind to receptors in a pseudo two-step mechanism of receptor activation. Exploitation of this structural knowledge has and will continue to provide important information for therapeutic strategies, as described in this review.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Kufareva
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Catherina L
authors.initials: CL
authors.lastname: Salanga
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
mesh_terms: D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes; D011487:Protein Conformation; D055503:Protein Multimerization; D019707:Receptors, Chemokine / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018925:Chemokines; D006025:Glycosaminoglycans; D046912:Multiprotein Complexes; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled