National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Bioessays. 2023 Sep;45(9):e2300057. doi: 10.1002/bies.202300057. Epub 2023 Jul 11.
Fold-switching proteins, which remodel their secondary and tertiary structures in response to cellular stimuli, suggest a new view of protein fold space. For decades, experimental evidence has indicated that protein fold space is discrete: dissimilar folds are encoded by dissimilar amino acid sequences. Challenging this assumption, fold-switching proteins interconnect discrete groups of dissimilar protein folds, making protein fold space fluid. Three recent observations support the concept of fluid fold space: (1) some amino acid sequences interconvert between folds with distinct secondary structures, (2) some naturally occurring sequences have switched folds by stepwise mutation, and (3) fold switching is evolutionarily selected and likely confers advantage. These observations indicate that minor amino acid sequence modifications can transform protein structure and function. Consequently, proteomic structural and functional diversity may be expanded by alternative splicing, small nucleotide polymorphisms, post-translational modifications, and modified translation rates.
构象转换蛋白可响应细胞刺激重塑其二级和三级结构，为人们提供了一种全新的蛋白质构象空间视角。数十年来，实验证据表明蛋白质构象空间是离散的：不同的折叠由不同的氨基酸序列编码。构象转换蛋白挑战了这一假设，它将不同的不相似蛋白质折叠组相互连接，使蛋白质构象空间具有流动性。最近有三个观察结果支持了流体构象空间的概念：（1）一些氨基酸序列在具有不同二级结构的折叠之间相互转换，（2）一些天然存在的序列通过逐步突变发生了折叠转换，（3）构象转换是进化选择的，并且可能带来优势。这些观察结果表明，较小的氨基酸序列修饰可以改变蛋白质的结构和功能。因此，通过选择性剪接、小核苷酸多态性、翻译后修饰和改变翻译速度等方式，蛋白质组的结构和功能多样性可能会得到扩展。
