Rational design of a peptide capture agent for CXCL8 based on a model of the CXCL8:CXCR1 complex
Helme, Dorothea (Technische Universität Darmstadt. Clemens-Schöpf-Institut)
Rink, Ina (Technische Universität Darmstadt. Clemens-Schöpf-Institut)
Dalton, James A. R.. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Brahm, Kevin (Technische Universität Darmstadt. Clemens-Schöpf-Institut)
Jöst, Marina (Technische Universität Darmstadt. Clemens-Schöpf-Institut)
Nargang, Tobias M. (Karlsruhe Institute of Technology. Institute of Microstructure Technology)
Blum, Witali (Technische Universität Darmstadt. Clemens-Schöpf-Institut)
Wadhwani, Parvesh (Karlsruhe Institute of Technology. Institute of Biological Interfaces)
Brenner-Weiss, Gerald (Karlsruhe Institute of Technology. Institute of Functional Interfaces)
Rapp, Bastian E. (Karlsruhe Institute of Technology. Institute of Microstructure Technology)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Schmitz, Katja (Technische Universität Darmstadt. Clemens-Schöpf-Institut)

Fecha:	2015
Resumen:	Protein-capture agents are widely used for the detection, immobilization and isolation of proteins and are the foundation for the development of in vitro diagnostic chips. The chemokine CXCL8 is an interesting protein target due to its involvement in the human inflammatory response. We constructed a novel structural model of CXCL8 interaction with its G-protein coupled receptor CXCR1, taking into account previously reported experimental data. From this CXCL8:CXCR1 model complex, the interaction of CXCL8 with residues near the extracellular domains 3 and 4 of CXCR1 were used as a scaffold for the rational design of a peptide capture agent called 'IL8RPLoops'. A molecular dynamics simulation of IL8RPLoops indicates a stable helical conformation consistent with the CXCR1 structure from which it was derived. CXCL8 capture in fluorescence-based assays on beads and on glass demonstrates that IL8RPLoops is an effective capture agent for CXCL8. Additionally, we found IL8RPLoops to be a potent inhibitor of CXCL8-induced neutrophil migration and CXCL8:CXCR1 association. A theoretical binding model for IL8RPLoops:CXCL8 is proposed, which shows the peptide predominantly interacting with CXCL8 via electrostatic contacts with the ELR motif at the CXCL8 N-terminus.
Derechos:	Tots els drets reservats.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Materia:	Rational design ; Peptide ; CXCL8 ; Capture-agent ; Chemokine ; GPCR ; CXCR1 ; Docking ; Receptor-ligand interaction ; Neutrophil migration
Publicado en:	RSC advances, Vol. 5 Núm. 33 (2015) , p. 25657-25668, ISSN 2046-2069

DOI: 10.1039/C4RA13749C

23 p, 1.5 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
Artículos > Artículos de investigación
Artículos > Artículos publicados