Song Jianxing
Department of Biological Sciences, Faculty of Science, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
Int J Mol Sci. 2024 Nov 28;25(23):12817. doi: 10.3390/ijms252312817.
Water exists in the beginning and hydrates all matter. Life emerged in water, requiring three essential components in compartmentalized spaces: (1) universal energy sources driving biochemical reactions and processes, (2) molecules that store, encode, and transmit information, and (3) functional players carrying out biological activities and structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as the universal energy currency, nucleic acids for genetic information storage and transmission, and phospholipids for cellular compartmentalization. Meanwhile, proteins composed of 20 α-amino acids have evolved into extremely diverse three-dimensional forms, including folded domains, intrinsically disordered regions (IDRs), and membrane-bound forms, to fulfill functional and structural roles. This review examines several unique findings: (1) insoluble proteins, including membrane proteins, can become solubilized in unsalted water, while folded cytosolic proteins can acquire membrane-inserting capacity; (2) Hofmeister salts affect protein stability by targeting hydration; (3) ATP biphasically modulates liquid-liquid phase separation (LLPS) of IDRs; (4) ATP antagonizes crowding-induced protein destabilization; and (5) ATP and triphosphates have the highest efficiency in inducing protein folding. These findings imply the following: (1) hydration might be encoded in protein sequences, central to manifestation and modulation of protein structures, dynamics, and functionalities; (2) phosphate anions have a unique capacity in enhancing μs-ms protein dynamics, likely through ionic state exchanges in the hydration shell, underpinning ATP, polyphosphate, and nucleic acids as molecular chaperones for protein folding; and (3) ATP, by linking triphosphate with adenosine, has acquired the capacity to spacetime-specifically release energy and modulate protein hydration, thus possessing myriad energy-dependent and -independent functions. In light of the success of AlphaFolds in accurately predicting protein structures by neural networks that store information as distributed patterns across nodes, a fundamental question arises: Could cellular networks also handle information similarly but with more intricate coding, diverse topological architectures, and spacetime-specific ATP energy supply in membrane-compartmentalized aqueous environments?
水自始便存在，并为所有物质提供水合作用。生命起源于水中，在分隔的空间中需要三个基本要素：（1）驱动生化反应和过程的通用能量来源；（2）存储、编码和传递信息的分子；（3）执行生物活动和进行结构组织的功能性成分。磷被选择用于生成三磷酸腺苷（ATP）作为通用能量货币、用于遗传信息存储和传递的核酸以及用于细胞分隔的磷脂。同时，由20种α-氨基酸组成的蛋白质已进化为极其多样的三维形式，包括折叠结构域、内在无序区域（IDR）和膜结合形式，以履行功能和结构作用。本综述探讨了几个独特的发现：（1）不溶性蛋白质，包括膜蛋白，可以在无盐水中溶解，而折叠的胞质蛋白可以获得膜插入能力；（2）霍夫迈斯特盐通过靶向水合作用影响蛋白质稳定性；（3）ATP对IDR的液-液相分离（LLPS）具有双相调节作用；（4）ATP拮抗拥挤诱导的蛋白质不稳定；（5）ATP和三磷酸盐在诱导蛋白质折叠方面效率最高。这些发现意味着：（1）水合作用可能编码在蛋白质序列中，是蛋白质结构、动力学和功能表现及调节的核心；（2）磷酸根阴离子具有增强微秒至毫秒级蛋白质动力学的独特能力，可能是通过水合壳中的离子状态交换，这使ATP、多磷酸盐和核酸成为蛋白质折叠的分子伴侣；（3）ATP通过将三磷酸与腺苷相连，获得了在时空上特异性释放能量和调节蛋白质水合作用的能力，从而具有无数依赖能量和不依赖能量的功能。鉴于AlphaFolds通过将信息存储为节点间分布式模式的神经网络准确预测蛋白质结构取得了成功，一个基本问题出现了：细胞网络是否也能以类似方式处理信息，但具有更复杂的编码、多样的拓扑结构以及在膜分隔的水环境中时空特异性的ATP能量供应？
