Deep sea osmolytes in action: their effect on protein–ligand binding under high pressure stress,Physical Chemistry Chemical Physics

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Deep sea osmolytes in action: their effect on protein–ligand binding under high pressure stress
Physical Chemistry Chemical Physics ( IF 2.9 ) Pub Date : 2022-06-24 , DOI: 10.1039/d2cp01769e
Armin Kamali ₁ , Nisrine Jahmidi-Azizi ₁ , Rosario Oliva ₂ , Roland Winter ₁

Affiliation

Because organisms living in the deep sea and in the sub-seafloor must be able to cope with hydrostatic pressures up to 1000 bar and more, their biomolecular processes, including ligand-binding reactions, must be adjusted to keep the associated volume changes low in order to function efficiently. Almost all organisms use organic cosolvents (osmolytes) to protect their cells from adverse environmental conditions. They counteract osmotic imbalance, stabilize the structure of proteins and maintain their function. We studied the binding properties of the prototypical ligand proflavine to two serum proteins with different binding pockets, BSA and HSA, in the presence of two prominent osmolytes, trimethylamine-N-oxide (TMAO) and glycine betaine (GB). TMAO and GB play an important role in the regulation and adaptation of life in deep-sea organisms. To this end, pressure dependent fluorescence spectroscopy was applied, supplemented by circular dichroism (CD) spectroscopy and computer modeling studies. The pressure-dependent measurements were also performed to investigate the intimate nature of the complex formation in relation to hydration and packing changes caused by the presence of the osmolytes. We show that TMAO and GB are able to modulate the ligand binding process in specific ways. Depending on the chemical make-up of the protein's binding pocket and thus the thermodynamic forces driving the binding process, there are osmolytes with specific interaction sites and binding strengths with water that are able to mediate efficient ligand binding even under external stress conditions. In the binding of proflavine to BSA and HSA, the addition of both compatible osmolytes leads to an increase in the binding constant upon pressurization, with TMAO being the most efficient, rendering the binding process also insensitive to pressurization even up to 2 kbar as the volume change remains close to zero. This effect can be corroborated by the effects the cosolvents impose on the strength and dynamics of hydration water as well as on the conformational dynamics of the protein.

中文翻译：

深海渗透物的作用：它们对高压胁迫下蛋白质-配体结合的影响

由于生活在深海和海底的生物必须能够应对高达 1000 巴甚至更高的静水压力，因此必须调整它们的生物分子过程，包括配体结合反应，以保持相关的体积变化低有效地发挥作用。几乎所有生物都使用有机助溶剂（渗透剂）来保护它们的细胞免受不利环境条件的影响。它们抵消渗透失衡，稳定蛋白质结构并维持其功能。我们研究了原型配体 proflavine 与两种具有不同结合口袋 BSA 和 HSA 的血清蛋白的结合特性，在两种主要的渗透物存在下，三甲胺-N-氧化物（TMAO）和甘氨酸甜菜碱（GB）。TMAO和GB在深海生物的生命调节和适应中发挥着重要作用。为此，应用了压力依赖性荧光光谱，并辅以圆二色 (CD) 光谱和计算机建模研究。还进行了与压力相关的测量，以研究与渗透物存在引起的水合和堆积变化相关的复合物地层的密切性质。我们表明 TMAO 和 GB 能够以特定方式调节配体结合过程。取决于蛋白质结合袋的化学组成以及驱动结合过程的热力学力，存在具有特定相互作用位点和与水结合强度的渗透物，即使在外部压力条件下也能够介导有效的配体结合。在 proflavine 与 BSA 和 HSA 的结合中，添加两种相容的渗透物会导致加压时结合常数的增加，其中 TMAO 是最有效的，使得结合过程对加压甚至高达 2 kbar 的体积也不敏感变化仍然接近于零。这种效应可以通过助溶剂对水合水的强度和动力学以及蛋白质构象动力学的影响得到证实。TMAO 是最有效的，即使在高达 2 kbar 的压力下，粘合过程也对压力不敏感，因为体积变化仍然接近于零。这种效应可以通过助溶剂对水合水的强度和动力学以及蛋白质构象动力学的影响得到证实。TMAO 是最有效的，即使在高达 2 kbar 的压力下，粘合过程也对压力不敏感，因为体积变化仍然接近于零。这种效应可以通过助溶剂对水合水的强度和动力学以及蛋白质构象动力学的影响得到证实。

更新日期：2022-06-24

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