Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR) family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD) simulations. A multi-steps binding mode is proposed: (i) the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii) hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR) motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii) electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.

No abstract

In this research, thermoresponsive and conductive fibers with core-sheath structure were fabricated by coaxial electrospinning. For preparing the spinning sheath solution, poly-(N-isopropylacrylamide-co-N-methylolacrylamide) (PNN) copolymer having thermoresponsive and cross-linkable properties was synthesized by free-radical polymerization using redox initiators; it was then mixed with the conductive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) at different weight ratios in water. On the other hand, poly(butyl acrylate-co-styrene) (PBS) copolymer synthesized by emulsion polymerization was dissolved in chloroform and used as the spinning core solution. After electrospinning, the fibers were treated at 110 8C for 1 h to cross-link the PNN portion in the sheath for strengthening the fibers. Well-defined core-sheath fibers were observed from SEM pictures; the outside and inside (core) diameters were 568 6 24 and 290 6 40 nm, respectively, as determined from TEM pictures. The fiber mats were further doped by DMSO to enhance their conductivity. For the fiber mat with the weight ratio of PEDOT:PSS/PNN at 0.20 in the sheath, its surface conductivity could reach 29.4 S/ cm. In addition, the fiber mats exhibited thermoresponsive properties that both swelling ratio and electric resistance decreased with temperature. Furthermore, the fiber mats exhibited improved flexibility as evaluated via bending test.