Biology Department, SUNY Buffalo State, 1300 Elmwood Ave, Buffalo, NY 14222, USA.
Int J Mol Sci. 2021 Mar 5;22(5):2615. doi: 10.3390/ijms22052615.
Glycine is an amino acid with unique properties because its side chain is composed of a single hydrogen atom. It confers conformational flexibility to proteins and conserved glycines are often indicative of protein domains involving tight turns or bends. All six beta-type connexins expressed in human epidermis (Cx26, Cx30, Cx30.3, Cx31, Cx31.1 and Cx32) contain a glycine at position 12 (G12). G12 is located about halfway through the cytoplasmic amino terminus and substitutions alter connexin function in a variety of ways, in some cases altering protein interactions and leading to cell death. There is also evidence that alteration of G12 changes the structure of the amino terminus in connexin- and amino acid- specific ways. This review integrates structural, functional and physiological information about the role of G12 in connexins, focusing on beta-connexins expressed in human epidermis. The importance of G12 substitutions in these beta-connexins is revealed in two hereditary skin disorders, keratitis ichthyosis and erythrokeratodermia variabilis, both of which result from missense mutations affecting G12.
甘氨酸是一种具有独特性质的氨基酸，因为其侧链由单个氢原子组成。它赋予蛋白质构象灵活性，并且保守的甘氨酸通常表明涉及紧密转弯或弯曲的蛋白质结构域。在人类表皮中表达的所有六种β型连接蛋白（Cx26、Cx30、Cx30.3、Cx31、Cx31.1 和 Cx32）在位置 12（G12）处都含有一个甘氨酸。G12 位于细胞质氨基末端的中间位置附近，取代会以各种方式改变连接蛋白的功能，在某些情况下会改变蛋白相互作用并导致细胞死亡。还有证据表明，G12 的改变以连接蛋白和氨基酸特异性的方式改变氨基末端的结构。本综述综合了关于 G12 在连接蛋白中的作用的结构、功能和生理信息，重点是在人类表皮中表达的β-连接蛋白。在两种遗传性皮肤疾病，鱼鳞癣和红斑角化症可变型中，G12 取代的重要性都得到了揭示，这两种疾病都是由影响 G12 的错义突变引起的。
