title: Sulfated glycosaminoglycans exploit the conformational plasticity of bone morphogenetic protein-2 (BMP-2) and alter the interaction profile with its receptor.
abstract: Sulfated glycosaminoglycans (GAGs) can direct cellular processes by interacting with proteins of the extracellular matrix (ECM). In this study we characterize the interaction profiles of chemically sulfated hyaluronan (HA) and chondroitin sulfate (CS) derivatives with bone morphogenetic protein-2 (BMP-2) and investigate their relevance for complex formation with the receptor BMPR-IA. These goals were addressed by surface plasmon resonance (SPR) and ELISA in combination with molecular modeling and dynamics simulation. We found not only the interaction of BMP-2 with GAGs to be dependent on the type and sulfation of GAGs but also BMP-2/GAG/BMPR-IA complex formation. The conformational plasticity of the BMP-2 N-termini plays a key role in the structural and thermodynamic characteristics of the BMP-2/GAG/BMPR-IA system. Hence we propose a model that provides direct insights into the importance of the structural and dynamical properties of the BMP-2/BMPR-IA system for its regulation by sulfated GAGs, in which structural asymmetry plays a key role.
authors.affiliation: Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden , Budapester Strasse 27, 01069 Dresden, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Samsonov
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Anselmi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.forename: Jana
authors.initials: J
authors.lastname: Becher
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pisabarro
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D015374:Biosensing Techniques; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000737:chemistry; D019295:Computational Biology; D005109:Extracellular Matrix / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D011487:Protein Conformation; D013816:Thermodynamics; D023822:Tissue Engineering
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D006025:Glycosaminoglycans; C013786:A73025; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D052005:Bone Morphogenetic Protein Receptors, Type I