Institut Pasteur, Unité de RMN des Biomolécules, Département de Biologie Structurale et Chimie, Paris, France; CNRS, UMR 3528, Paris, France; Université Pierre et Marie Curie, Cellule Pasteur UPMC, Paris, France.
Institut Pasteur, Unité de RMN des Biomolécules, Département de Biologie Structurale et Chimie, Paris, France; CNRS, UMR 3528, Paris, France.
PLoS One. 2014 Apr 11;9(4):e89502. doi: 10.1371/journal.pone.0089502. eCollection 2014.
Bacteria use diverse signaling pathways to control gene expression in response to external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed by an outer membrane transporter. This signal is then transmitted to an antisigma factor and subsequently to the cytoplasm where an ECF sigma factor induces expression of genes related to the acquisition of this nutrient. The molecular interactions involved in this transmembrane signaling are poorly understood and structural data on this family of antisigma factor are rare. Here, we present the first structural study of the periplasmic domain of an antisigma factor and its interaction with the transporter. The study concerns the signaling in the heme acquisition system (Has) of Serratia marcescens. Our data support unprecedented partially disordered periplasmic domain of an anti-sigma factor HasS in contact with a membrane-mimicking environment. We solved the 3D structure of the signaling domain of HasR transporter and identified the residues at the HasS-HasR interface. Their conservation in several bacteria suggests wider significance of the proposed model for the understanding of bacterial transmembrane signaling.
细菌利用多种信号通路来响应外部刺激控制基因表达。在革兰氏阴性菌中，营养物质的结合由外膜转运蛋白感知。然后，该信号被传递给反西格玛因子，然后传递到细胞质，其中 ECF 西格玛因子诱导与获取该营养物质相关的基因表达。这个跨膜信号转导中涉及的分子相互作用还不太清楚，并且这个反西格玛因子家族的结构数据也很少。在这里，我们首次研究了反西格玛因子的周质域及其与转运蛋白的相互作用。该研究涉及粘质沙雷氏菌血红素获取系统 (Has) 的信号转导。我们的数据支持反西格玛因子 HasS 的前所未有的部分无序周质域与模拟膜环境接触。我们解决了 HasR 转运蛋白信号域的 3D 结构，并确定了 HasS-HasR 界面上的残基。它们在几种细菌中的保守性表明，所提出的模型对于理解细菌跨膜信号转导具有更广泛的意义。
