Zerbib D, Prentki P, Gamas P, Freund E, Galas D J, Chandler M
Centre de Recherche de Biochimie et Génétique Cellulaire du CNRS, Toulouse, France.
Mol Microbiol. 1990 Sep;4(9):1477-86.
The IS 1-encoded protein InsA binds specifically to both ends of IS1, and acts as a repressor of IS1 gene expression and may be a direct inhibitor of the transposition process. We show here, using DNasel 'foot-printing' and gel retardation, that the InsA binding sites are located within the 24/25 bp minimal active ends of IS1 and that InsA induces DNA bending upon binding. Conformational modification of the ends of IS1 as a result of binding of the host protein integration host factor (IHF) to its site within the minimal ends has been previously observed. Using a collection of synthetic mutant ends we have mapped some of the nucleotide sequence requirements for InsA binding and for transposition activity. We show that sequences necessary for InsA binding are also essential for transposition activity. We demonstrate that InsA and IHF binding sites overlap since some sequence determinants are shared by both InsA and IHF. The data suggest that these ends contain two functional domains: one for binding of InsA and IHF, and the other for transposition activity. A third region, when present, may enhance transposition activity with an intact right end. This 'architecture' of the ends of IS1 is remarkably similar to that of IS elements IS10, IS50 and IS903.
由IS1编码的蛋白质InsA能特异性结合IS1的两端,并作为IS1基因表达的阻遏物,可能是转座过程的直接抑制剂。我们在此利用DNA酶I足迹法和凝胶阻滞实验表明,InsA的结合位点位于IS1的24/25bp最小活性末端内,且InsA结合时会诱导DNA弯曲。此前已观察到,宿主蛋白整合宿主因子(IHF)与其在最小末端内的位点结合会导致IS1末端的构象改变。我们利用一系列合成突变末端,确定了InsA结合和转座活性所需的一些核苷酸序列要求。我们发现,InsA结合所需的序列对转座活性也至关重要。我们证明InsA和IHF的结合位点重叠,因为InsA和IHF共享一些序列决定因素。数据表明,这些末端包含两个功能域:一个用于InsA和IHF的结合,另一个用于转座活性。当存在第三个区域时,可能会增强完整右端的转座活性。IS1末端的这种“结构”与IS元件IS10、IS50和IS903的结构非常相似。