Structural basis for differential binding of the interleukin-8 monomer and dimer to the CXCR1 N-domain: role of coupled interactions and dynamics.

ABSTRACT: Interleukin-8 (IL-8 or CXCL8) plays a critical role in orchestrating the immune response by binding and activating the receptor CXCR1 that belongs to the GPCR class. IL-8 exists as both monomers and dimers, and both bind CXCR1 but with differential affinities. It is well established that the monomer is the high-affinity ligand and that the interactions between the ligand N-loop and receptor N-domain play a critical role in determining binding affinity. In order to characterize the structural basis of differential binding of the IL-8 monomer and dimer to the CXCR1 N-domain, we analyzed binding-induced NMR chemical shift and peak intensity changes and show that they are exquisitely sensitive and can provide detailed insights into the binding process. We used three IL-8 variants, a designed m

SUBMITTER: Ravindran A 

PROVIDER: S-EPMC2858980 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature