Sulfated glycosaminoglycans exploit the conformational plasticity of bone morphogenetic protein-2 (BMP-2) and alter the interaction profile with its receptor
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 3083-3092 |
Seitenumfang | 10 |
Fachzeitschrift | Biomacromolecules |
Jahrgang | 15 |
Ausgabenummer | 8 |
Publikationsstatus | Veröffentlicht - 11 Aug. 2014 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 84905841944 |
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ORCID | /0000-0002-5611-9903/work/142244037 |
Schlagworte
Schlagwörter
- Biocompatible Materials/chemistry, Biosensing Techniques, Bone Morphogenetic Protein 2/chemistry, Bone Morphogenetic Protein Receptors, Type I/chemistry, Chondroitin Sulfates/chemistry, Computational Biology, Extracellular Matrix/chemistry, Glycosaminoglycans/chemistry, Humans, Hyaluronic Acid/chemistry, Protein Conformation, Thermodynamics, Tissue Engineering