Reichenwallner Jörg, Michler Sebastian, Schwieger Christian, Hinderberger Dariush
Institute of Chemistry, Physical Chemistry - Complex Self-Organizing Systems, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120 Halle (Saale), Germany.
Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
J Phys Chem B. 2025 Apr 10;129(14):3571-3589. doi: 10.1021/acs.jpcb.4c08717. Epub 2025 Mar 26.
Using an electron paramagnetic resonance (EPR) spectroscopic strategy that has been developed for core-shell polymers, the complexity of the binding of fatty acids to human serum albumin (HSA) is characterized in detail. We unravel the internal dynamics of HSA solutions with fatty acids by applying continuous wave EPR (CW EPR) from which we derive a consistent thermodynamic interpretation about fatty acid interactions with HSA in the investigated temperature range of 5-97 °C. Additionally, data from CW EPR are corroborated by dynamic light scattering (DLS), differential scanning calorimetry (DSC) and nanoscale distance measurements using double electron-electron resonance (DEER) spectroscopy. We discuss our data in light of decades of biophysical studies on albumin and aim at drawing a complete functional and dynamic picture of HSA "at work". This picture suggests that HSA is built from modular, rotationally decoupled domains that resemble an entangled three-piece in solution.
利用一种针对核壳聚合物开发的电子顺磁共振（EPR）光谱策略，详细表征了脂肪酸与人类血清白蛋白（HSA）结合的复杂性。我们通过应用连续波EPR（CW EPR）来揭示含有脂肪酸的HSA溶液的内部动力学，从中我们得出了在5 - 97°C的研究温度范围内脂肪酸与HSA相互作用的一致热力学解释。此外，CW EPR的数据通过动态光散射（DLS）、差示扫描量热法（DSC）以及使用双电子 - 电子共振（DEER）光谱的纳米级距离测量得到了证实。我们根据几十年来关于白蛋白的生物物理研究来讨论我们的数据，旨在描绘出HSA“工作时”完整的功能和动态图景。这幅图景表明，HSA由模块化的、旋转解耦的结构域组成，在溶液中类似于一个纠缠在一起的三件套。
