Oberer Monika, Zangger Klaus, Gruber Karl, Keller Walter
Institut für Chemie, Arbeitsgruppe Strukturbiologie, Karl-Franzens-Universität Graz, A-8010 Graz, Austria.
Protein Sci. 2007 Aug;16(8):1676-88. doi: 10.1110/ps.062680707.
ParD is the antidote of the plasmid-encoded toxin-antitoxin (TA) system ParD-ParE. These modules rely on differential stabilities of a highly expressed but labile antidote and a stable toxin expressed from one operon. Consequently, loss of the coding plasmid results in loss of the protective antidote and poisoning of the cell. The antidote protein usually also exhibits an autoregulatory function of the operon. In this paper, we present the solution structure of ParD. The repressor activity of ParD is mediated by the N-terminal half of the protein, which adopts a ribbon-helix-helix (RHH) fold. The C-terminal half of the protein is unstructured in the absence of its cognate binding partner ParE. Based on homology with other RHH proteins, we present a model of the ParD-DNA interaction, with the antiparallel beta-strand being inserted into the major groove of DNA. The fusion of the N-terminal DNA-binding RHH motif to the toxin-binding unstructured C-terminal domain is discussed in its evolutionary context.
ParD是质粒编码的毒素-抗毒素（TA）系统ParD-ParE的抗毒素。这些模块依赖于一个高表达但不稳定的抗毒素和一个从一个操纵子表达的稳定毒素的不同稳定性。因此，编码质粒的丢失会导致保护性抗毒素的丧失和细胞中毒。抗毒素蛋白通常还表现出操纵子的自调节功能。在本文中，我们展示了ParD的溶液结构。ParD的阻遏活性由蛋白质的N端介导，其采用带状-螺旋-螺旋（RHH）折叠。在没有其同源结合伙伴ParE的情况下，蛋白质的C端是无结构的。基于与其他RHH蛋白的同源性，我们提出了一个ParD与DNA相互作用的模型，其中反平行β链插入DNA的大沟中。在进化背景下讨论了N端DNA结合RHH基序与毒素结合无结构C端结构域的融合。
