title: Characterization of the interaction of interleukin-8 with hyaluronan, chondroitin sulfate, dermatan sulfate and their sulfated derivatives by spectroscopy and molecular modeling.
abstract: The interactions between glycosaminoglycans (GAGs), important components of the extracellular matrix, and proteins such as growth factors and chemokines play critical roles in cellular regulation processes. Therefore, the design of GAG derivatives for the development of innovative materials with bio-like properties in terms of their interaction with regulatory proteins is of great interest for tissue engineering and regenerative medicine. Previous work on the chemokine interleukin-8 (IL-8) has focused on its interaction with heparin and heparan sulfate, which regulate chemokine function. However, the extracellular matrix contains other GAGs, such as hyaluronic acid (HA), dermatan sulfate (DS) and chondroitin sulfate (CS), which have so far not been characterized in terms of their distinct molecular recognition properties towards IL-8 in relation to their length and sulfation patterns. NMR and molecular modeling have been in great part the methods of choice to study the structural and recognition properties of GAGs and their protein complexes. However, separately these methods have challenges to cope with the high degree of similarity and flexibility that GAGs exhibit. In this work, we combine fluorescence spectroscopy, NMR experiments, docking and molecular dynamics simulations to study the configurational and recognition properties of IL-8 towards a series of HA and CS derivatives and DS. We analyze the effects of GAG length and sulfation patterns in binding strength and specificity, and the influence of GAG binding on IL-8 dimer formation. Our results highlight the importance of combining experimental and theoretical approaches to obtain a better understanding of the molecular recognition properties of GAG-protein systems.
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, D-04107 Leipzig, Germany.
authors.forename: Annelie
authors.initials: A
authors.lastname: Pichert
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Samsonov
authors.forename: Stephan
authors.initials: S
authors.lastname: Theisgen
authors.forename: Lars
authors.initials: L
authors.lastname: Thomas
authors.forename: Lars
authors.initials: L
authors.lastname: Baumann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pisabarro
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006860:Hydrogen Bonding; D016209:Interleukin-8 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D016209:Interleukin-8; D003871:Dermatan Sulfate; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates