Sulfated Glycosaminoglycans Exploit the Conformational Plasticity of Bone Morphogenetic Protein-2 (BMP-2) and Alter the Interaction Profile with Its Receptor
Sulfated Glycosaminoglycans Exploit the Conformational Plasticity of Bone Morphogenetic Protein-2 (BMP-2) and Alter the Interaction Profile with Its Receptor
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DOI：
10.1021/bm5006855
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发表时间：
2014-08-01
影响因子：
6.2
通讯作者：
Pisabarro, M. Teresa
中科院分区：
文献类型：
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作者：
Hintze, Vera;Samsonov, Sergey A.;Pisabarro, M. Teresa
巯基糖胺聚糖（GAGs）可以通过与细胞外基质（ECM）蛋白相互作用来指导细胞过程。在这项研究中，我们描述了化学硫酸酸化透明质酸（HA）和硫酸软骨素（CS）衍生物与骨形态发生蛋白-2 （BMP-2）的相互作用，并研究了它们与受体BMPR-IA形成复合物的相关性。这些目标通过表面等离子体共振（SPR）和ELISA结合分子建模和动力学模拟来解决。我们发现BMP-2与GAGs的相互作用不仅取决于GAGs的类型和硫化程度，还取决于BMP-2/GAG/BMPR-IA复合物的形成。BMP-2 n端构象的可塑性在BMP-2/GAG/ bmp - ia体系的结构和热力学特性中起着关键作用。因此，我们提出了一个模型，提供了对BMP-2/BMPR-IA系统的结构和动力学特性的重要性的直接见解，其中结构不对称起着关键作用。
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.