透明质酸-精氨酸增强相互作用源于独特的分子特征：改善的静电作用与侧链特异性
Hyaluronan-Arginine Enhanced Interaction Emerges from Distinctive Molecular Signature with Improved Electrostatics and Side-Chain Specificity
AI总结：
本研究通过NMR和分子动力学模拟揭示了透明质酸与蛋白质（尤其是精氨酸）的动态结合机制，发现静电作用和侧链特异性是精氨酸与透明质酸强结合的关键。
AI中文摘要：
透明质酸是一种存在于质膜外的糖聚合物，是细胞外基质（ECM）支架的关键成分。透明质酸的长度和适度的负电荷有助于ECM的缠结和溶解性。这使其能够有效促进凝胶状条件的形成，这对于支持和保护各种组织中的细胞至关重要。作为多种蛋白质的已知配体，理解其与各种氨基酸的相互作用有助于阐明其生物学功能。本研究采用NMR和分子动力学模拟（MD）来探索透明质酸-蛋白质相互作用的潜在一般分子机制。我们检测了短精氨酸、赖氨酸或甘氨酸寡肽与透明质酸多糖的结合，使用化学位移扰动（CSP）检测肽滴定后透明质酸1H NMR光谱的变化。CSP有助于识别具体的结合区域，并提供关于肽相对相互作用强度的见解。我们还使用核Overhauser效应（NOE）测量来识别潜在的稳定透明质酸-肽复合物。然而，缺乏NOE信号并不支持形成强且明确的复合物。正CSP信号与负NOE的结合提示了一种动态结合模式，而无稳定复合物形成，MD进一步支持了这一点。精氨酸作为一种带正电荷的氨基酸，与带负电荷的透明质酸表现出最强的结合力，带相似电荷的赖氨酸远远位居第二，突出了静电作用和侧链特异性在这些相互作用中的重要性。透明质酸的羧基和酰胺基团驱动其与肽的相互作用，并通过氢键进一步稳定。我们的发现阐明了透明质酸-蛋白质相互作用模式（通常涉及精氨酸），并突出了精氨酸在蛋白质识别透明质酸中的关键作用。
英文摘要：
Hyaluronan, a sugar polymer found outside the plasma membrane, is a critical component of the extracellular matrix (ECM) scaffold. Hyaluronan's length and moderate negative charge aid in ECM entanglement and solubility. This allows it to effectively foster gel-like conditions, which are critical for supporting and protecting cells in various tissues. As a recognized ligand for multiple proteins, understanding its interaction with various amino acids helps elucidate its biological functions. This study employs NMR and molecular dynamics simulations (MD) to explore a potential general molecular mechanism for hyaluronan-protein interactions. We examine the binding of short arginine, lysine, or glycine oligopeptides to hyaluronan polysaccharides, using chemical shift perturbation (CSP) to detect changes in hyaluronan's 1H NMR spectra upon peptide titration. CSP helps to identify concrete binding regions and offers insights into the relative interaction strength of the peptides. We also use nuclear Overhauser effect (NOE) measurements to identify a potentially stable hyaluronan-peptide complex. However, the lack of NOE signals does not support the formation of strong and defined complexes. The combination of a positive CSP signal and negative NOE suggests a dynamic binding mode without stable complex formation, which MD further supports. Arginine, a positively charged amino acid, exhibits the strongest binding to the negatively charged hyaluronan, with the similarly charged lysine coming in distant second, highlighting the significance of electrostatics and side-chain specificity in these interactions. Hyaluronan's carboxyl and amide groups drive its interaction with the peptides, further stabilized by hydrogen bonds. Our findings elucidate hyaluronan-protein interaction patterns, typically involving arginine, and highlight arginine's crucial role in hyaluronan recognition by proteins.
