Crystal Structure of the Immunity Protein and its Complex with Colicin E3

Colicin E3是一种有毒蛋白质，由某些菌株分泌，以消除生活在同一生态位中的相关菌株。Colicin E3通过在特定位置划破16S核糖体RNA来使受感染细胞的蛋白质生物合成机制失活。因此，Colicin E3在酶的作用下是一种内切核酸酶。产生的生物体通过一种与结肠素E3结合的“免疫蛋白”对其自身的结肠素E3的毒性免疫，从而使其失去活性。Shoham博士提出了结肠素E3及其抑制剂的晶体结构测定方法，从分子水平上了解了结肠素E3的核糖核酸酶作用及其对免疫蛋白的抑制作用。对酶-抑制物相互作用的详细了解也将有助于了解切割部位附近的整个核糖体的结构。免疫蛋白是为数不多的已知的核糖核酸酶抑制剂之一。它的三维结构可能为设计其他具有所需特异性的核糖核酸酶抑制剂提供基础。

Colicin E3 is a toxic protein secreted by certain strains of E. coli in order to eliminate related strains of bacterial living in the same ecological niche. Colicin E3 inactivates the protein biosynthetic machinery of the infected cell by nicking 16S ribosomal RNA at a specific site. Colicin E3 thus acts enzymatically as an endoribonuclease. The producing organism is immune to the toxicity of its own colicin E3 by virtue of a "immunity protein" which binds to colicin E3 and thus renders it inactive. Dr. Shoham proposed a crystallographic structure determination of colicin E3 and its inhibitor, the immunity protein gain understanding at the molecular level of the ribonuclease action of colicin E3 and its inhibition of immunity protein. Detailed knowledge of the enzyme-inhibitor interactions will also shed light on the structure of the ribosome at large, in the vicinity of the cutting site. the immunity protein is one the very few known ribonuclease inhibitors. Its three-dimensional structure may provide a basis for the design of other RNAse inhibitors with desired specificity.