大肠杆菌(Escherichia coli)LexA蛋白的结构与功能

Structure and Functions of the Escherichia coli LexA Protein

LexA蛋白首先在大肠杆菌(Escherichia coli)中作为SOS反应的重要调节因子之一被发现.LexA蛋白含有202个氨基酸,由N端DNA结合结构域和C端催化核心结构域构成.细胞中LexA蛋白大都以二聚体形式存在,并且有可切割和不可切割两种构象.在正常生理条件下,LexA特异性结合16 bp的保守序列5'-CTGTN8ACAG-3',即SOS盒,抑制约50个基因的表达.当发生DNA损伤时,活化的RecA蛋白通过稳定LexA蛋白可切割构象,促进LexA蛋白Ala84-Gly85间肽键的切割,产生的C端LexA85-202和N端LexA1-84被蛋白酶ClpXP和Lon快速降解.LexA蛋白切割后,SOS基因以一定的顺序开始表达,并且完成DNA损伤修复.本文回顾和总结了LexA蛋白分子结构,自我切割分子机制和影响因素,以及在SOS反应中的作用等方面的研究进展.同时,也讨论了LexA蛋白在原核细胞中的进化保守性.

The LexA protein in Escherichia coli was first discovered as a major regulator of the SOS response. The 22.3 kD protein is composed of 202 amino acids residues to form a DNA-binding domain and a catalytic core domain. LexA is predominantly existed in dimers of either cleavable or non-cleavable conformations in cells. Under normal physical conditions, LexA specifically binds to a 16 bp consensus palindrome of 5＇-CTGTNsACAG-3＇, known as the SOS box, and represses the expression of about 50 genes. When DNA damage occurs, the autocleavage of LexA at the A84-G85 peptide bond from the stabilized cleavable conformation induces the sequential expression of SOS genes for DNA repairs. The cleaved C-terminal LexA85-202 and N-terminal LexA1-84 fragments are quickly degreded by ClpXP and Lon proteases. In this review, the LexA protein structure with the evolutionary conservation, the molecular mechanism of its autocleavage, and its role in SOS response were discussed.