The S100 genes encode a conserved group of 21 vertebrate‐specific EF‐hand calcium‐binding proteins. Since their discovery in 1965, S100 proteins have remained enigmatic in terms of their cellular functions. In this review, we summarize the calcium‐ and zinc‐binding properties of the dimeric S100B and S100A1 proteins and highlight data that shed new light on the extracellular and intracellular regulation and functions of S100B. We point out that S100B and S100A1 homodimers are not functionally interchangeable and that in a S100A1/S100B heterodimer, S100A1 acts as a negative regulator for the ability of S100B to bind Zn2+. The Ca2+ and Zn2+‐dependent interactions of S100B with a wide array of proteins form the basis of its activities and have led to the derivation of some initial rules for S100B recognition of protein targets. However, recent findings have strongly suggested that these rules need to be revisited. Here, we describe a new consensus S100B binding motif present in intracellular and extracellular vertebrate‐specific proteins and propose a new model for stable interactions of S100B dimers with full‐length target proteins. A chaperone‐associated function for intracellular S100B in adaptive cellular stress responses is also discussed. This review may help guide future studies on the functions of S100 proteins in general.

中文翻译：

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结合 Zn 2+ 和 Ca 2+ 的 S100B 和 S100A1 蛋白：超越神话

S100 基因编码一组保守的 21 种脊椎动物特异性 EF 手钙结合蛋白。自 1965 年发现以来，S100 蛋白在其细胞功能方面一直是个谜。在这篇综述中，我们总结了二聚体 S100B 和 S100A1 蛋白的钙和锌结合特性，并强调了揭示 S100B 的细胞外和细胞内调节和功能的新数据。我们指出 S100B 和 S100A1 同源二聚体在功能上不可互换，并且在 S100A1/S100B 异源二聚体中，S100A1 作为 S100B 结合 Zn2+ 的能力的负调节器。S100B 与多种蛋白质的 Ca2+ 和 Zn2+ 依赖性相互作用构成了其活性的基础，并导致了 S100B 识别蛋白质靶标的一些初始规则的推导。然而，最近的调查结果强烈表明需要重新审视这些规则。在这里，我们描述了存在于细胞内和细胞外脊椎动物特异性蛋白中的新的共有 S100B 结合基序，并提出了一种新模型，用于 S100B 二聚体与全长靶蛋白的稳定相互作用。还讨论了细胞内 S100B 在适应性细胞应激反应中的分子伴侣相关功能。该综述可能有助于指导未来对 S100 蛋白功能的总体研究。还讨论了细胞内 S100B 在适应性细胞应激反应中的分子伴侣相关功能。该综述可能有助于指导未来对 S100 蛋白功能的总体研究。还讨论了细胞内 S100B 在适应性细胞应激反应中的分子伴侣相关功能。该综述可能有助于指导未来对 S100 蛋白功能的总体研究。