Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, China.
The Central Laboratory, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518035, China.
Molecules. 2021 Mar 4;26(5):1372. doi: 10.3390/molecules26051372.
MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in , which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (), whereas MsrBs can only function on the L-Met-O epimer in proteins. Though there are isomerases existent that could transfer L-Met-O to L-Met-O and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.
MsrB1 曾被命名为硒蛋白 R，因为它最初是通过在人类基因组中搜索硒代半胱氨酸插入序列 (SECIS) 而被鉴定为含有硒代半胱氨酸的蛋白质。后来，人们发现 MsrB1 与 中的 PilB 同源，后者是一种甲硫氨酸亚砜还原酶 (Msr)，专门还原蛋白质中的 L-甲硫氨酸亚砜 (L-Met-O)。在人类和小鼠中，有四个成员构成了 Msr 家族，分别是 MsrA、MsrB1、MsrB2 和 MsrB3。MsrA 可以还原游离或含蛋白质的 L-Met-O ()，而 MsrBs 只能在蛋白质中的 L-Met-O 差向异构体上发挥作用。尽管存在可以将 L-Met-O 转化为 L-Met-O 或反之的异构酶，但 Msr 的缺失会导致小鼠模型出现不同的表型。这些观察结果表明，一个 Msr 的功能不能完全由另一个 Msr 来补充。在哺乳动物的 Msrs 中，MsrB1 是唯一含有硒代半胱氨酸的蛋白质，我们最近发现 MsrB1 的缺失会扰乱小鼠的突触可塑性，并伴随着大脑中的星形胶质细胞增生。在这篇综述中，我们总结了 Msr 缺乏和硒在中枢神经系统中的生物活性所带来的影响，特别是我们从 MsrB1 敲除小鼠模型中学到的内容。我们希望这将有助于更好地理解痕量元素硒如何参与 L-Met-O 的还原，并参与神经生物学。
