Zheng Zejun, Goncearenco Alexander, Berezovsky Igor N
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01, Matrix, 138671, Singapore.
VantAI, 151 W 42nd Street, New York, NY, 10036, United States.
Curr Res Struct Biol. 2024 Apr 9;7:100142. doi: 10.1016/j.crstbi.2024.100142. eCollection 2024.
Binding of nucleotides and their derivatives is one of the most ancient elementary functions dating back to the Origin of Life. We review here the works considering one of the key elements in binding of (di)nucleotide-containing ligands - phosphate binding. We start from a brief discussion of major participants, conditions, and events in prebiotic evolution that resulted in the Origin of Life. Tracing back to the basic functions, including metal and phosphate binding, and, potentially, formation of primitive protein-protein interactions, we focus here on the phosphate binding. Critically assessing works on the structural, functional, and evolutionary aspects of phosphate binding, we perform a simple computational experiment reconstructing its most ancient and generic sequence prototype. The profiles of the phosphate binding signatures have been derived in form of position-specific scoring matrices (PSSMs), their peculiarities depending on the type of the ligands have been analyzed, and evolutionary connections between them have been delineated. Then, the apparent prototype that gave rise to all relevant phosphate-binding signatures had also been reconstructed. We show that two major signatures of the phosphate binding that discriminate between the binding of dinucleotide- and nucleotide-containing ligands are GxGxxG and GxxGxG, respectively. It appears that the signature archetypal for dinucleotide-containing ligands is more generic, and it can frequently bind phosphate groups in nucleotide-containing ligands as well. The reconstructed prototype's key signature GxGGxG underlies the role of glycine residues in providing flexibility and interactions necessary for binding the phosphate groups. The prototype also contains other ancient amino acids, valine, and alanine, showing versatility towards evolutionary design and functional diversification.
核苷酸及其衍生物的结合是可追溯到生命起源的最古老的基本功能之一。在此，我们回顾了一些研究工作，这些工作涉及含（二）核苷酸配体结合中的一个关键要素——磷酸盐结合。我们首先简要讨论了导致生命起源的前生物进化中的主要参与者、条件和事件。追溯到包括金属和磷酸盐结合以及可能的原始蛋白质 - 蛋白质相互作用形成在内的基本功能，我们在此聚焦于磷酸盐结合。批判性地评估关于磷酸盐结合的结构、功能和进化方面的研究工作，我们进行了一个简单的计算实验，重建其最古老和通用的序列原型。磷酸盐结合特征的图谱以位置特异性评分矩阵（PSSM）的形式得出，分析了它们因配体类型而异的特点，并描绘了它们之间的进化联系。然后，还重建了产生所有相关磷酸盐结合特征的明显原型。我们表明，区分含二核苷酸和含核苷酸配体结合的磷酸盐结合的两个主要特征分别是GxGxxG和GxxGxG。似乎含二核苷酸配体的特征原型更具通用性，它也能频繁结合含核苷酸配体中的磷酸基团。重建原型的关键特征GxGGxG是甘氨酸残基在提供结合磷酸基团所需的灵活性和相互作用方面发挥作用的基础。该原型还包含其他古老的氨基酸，缬氨酸和丙氨酸，显示出在进化设计和功能多样化方面的多功能性。
