断裂蛋白质内含子的剪接机制、起源和进化

蛋白质内含子(intein)是具有自我催化活性的蛋白质. 翻译后，通过蛋白质剪接从蛋白质前体中去掉，并以肽键连接两侧蛋白质外显子(extein)形成成熟蛋白质. 断裂蛋白质内含子(split intein)在蛋白质内含子中部区域特定位点发生断裂，形成N端片段和C端片段，分别由基因组上相距较远的两个基因编码. 现在已知,它仅分布于蓝细菌和古细菌中. 断裂蛋白质内含子的N端片段和C端片段通过非共价键(如静电作用)相互识别，重建催化活性中心，介导蛋白质反式剪接. 断裂蛋白质内含子的发现进一步深化了人们对基因表达和蛋白质翻译后成熟过程复杂性的认识，而且它在蛋白质工程、蛋白质药物开发和蛋白质结构与功能研究等方面有非常广泛的应用. 本文试图综述断裂蛋白质内含子的分布、结构特征和剪接机制，并分析其可能的起源和进化途径.

Split Intein: Splicing Mechanism, Origin and Evolution

The intein is autocatalytic protein domain that post translationally excises from protein precursor and concomitantly ligates its flanking exteins with a peptide bond in a process called protein splicing. An intein containing protein can be split inside its intein domain and two parts of the protein encoded by two separate genes located apart in the genome, respectively. The N terminal region of the protein consists of an N extein sequence followed by an N intein sequence, whereas the C terminal region consists of a C intein sequence followed by a C extein sequence. The N and C terminal inteins rapidly self associate and reconstitute protein trans splicing activity. Two parts of split intein associate by non covalent bonds (such as electrostatic interaction) with high affinity. To date, split intein was only found in some cyanobacteria and archaebacteria genomes. Further, the discovery of split intein suggests that the gene expression and protein post translational processing are more complicated. Understanding the mechanism of split intein splicing pathway has led to the development of many applications in the fields of protein engineering, development of protein drug and research of protein structure and function. This review provides a survey of recent insights of distribution, structure and splicing mechanism of split intein, as well as its possible origin and evolution.