Structural basis of chemokine receptor function--a model for binding affinity and ligand selectivity.
Chemokine receptors play fundamental roles in human physiology from embryogenesis to inflammatory response. The receptors belong to the G-protein coupled receptor class, and are activated by chemokine ligands with a range of specificities and affinities that result in a complicated network of interactions. The molecular basis for function is largely a black box, and can be directly attributed to the lack of structural information on the receptors. Studies to date indicate that function can be best described by a two-site model, that involves interactions between the receptor N-domain and ligand N-terminal loop residues (site-I), and between receptor extracellular loop and the ligand N-terminal residues (site-II). In this review, we describe how the two-site model could modulate binding affinity and ligand selectivity, and also highlight some of the unique chemokine receptor features, and their role in function.
Rajagopalan
Lavanya
L
Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology, The University of Texas Medical Branch, Galveston, TX 77555-1055, USA.
Rajarathnam
Krishna
K
D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019707:Receptors, Chemokine / Q000737:chemistry* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D008024:Ligands; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled