AbstractThree‐dimensional (3D) structure information, now available at the proteome scale, may facilitate the detection of remote evolutionary relationships in protein superfamilies. Here, we illustrate this with the identification of a novel family of protein domains related to the ferredoxin‐like superfold, by combining (i) transitive sequence similarity searches, (ii) clustering approaches, and (iii) the use of AlphaFold2 3D structure models. Domains of this family were initially identified in relation with the intracellular biomineralization of calcium carbonates by Cyanobacteria. They are part of the large heavy‐metal‐associated (HMA) superfamily, departing from the latter by specific sequence and structural features. In particular, most of them share conserved basic amino acids (hence their name CoBaHMA for Conserved Basic residues HMA), forming a positively charged surface, which is likely to interact with anionic partners. CoBaHMA domains are found in diverse modular organizations in bacteria, existing in the form of monodomain proteins or as part of larger proteins, some of which are membrane proteins involved in transport or lipid metabolism. This suggests that the CoBaHMA domains may exert a regulatory function, involving interactions with anionic lipids. This hypothesis might have a particular resonance in the context of the compartmentalization observed for cyanobacterial intracellular calcium carbonates.

中文翻译：

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AlphaFold2 引导的 CoBaHMA 描述，CoBaHMA 是重金属相关超家族中的一个新的细菌结构域家族

摘要三维（3D）结构信息现在可在蛋白质组规模上使用，可能有助于检测蛋白质超家族中的远程进化关系。在这里，我们通过结合 (i) 传递序列相似性搜索、(ii) 聚类方法和 (iii) AlphaFold2 3D 结构模型的使用，识别与铁氧还蛋白样超折叠相关的新型蛋白质结构域家族来说明这一点。该家族的结构域最初是与蓝藻细胞内碳酸钙生物矿化相关的。它们是重金属相关（HMA）大家族的一部分，但在特定的序列和结构特征上与后者不同。特别是，它们中的大多数共享保守的碱性氨基酸（因此它们被称为 CoBaHMA）钴服务的巴碳化硅残留物健康管理协会），形成带正电的表面，可能与阴离子伙伴相互作用。CoBaHMA 结构域存在于细菌的不同模块组织中，以单结构域蛋白的形式存在或作为较大蛋白的一部分存在，其中一些是参与运输或脂质代谢的膜蛋白。这表明 CoBaHMA 结构域可能发挥调节功能，涉及与阴离子脂质的相互作用。这一假设可能在观察到蓝藻细胞内碳酸钙的区室化背景下产生特殊的共鸣。