The histidine kinase CusS senses silver ions through direct binding by its sensor domain

The Cus system of Escherichia coli aids in protection of cells from high concentrations of Ag(I) and Cu(I). The histidine kinase CusS of the CusRS two-component system functions as a Ag(I)/Cu(I)-responsive sensor kinase and is essential for induction of the genes encoding the CusCFBA efflux pump. In this study, we have examined the molecular features of the sensor domain of CusS in order to understand how a metal-responsive histidine kinase senses specific metal ions. We find that the predicted periplasmic sensor domain of CusS directly interacts with Ag(I) ions and undergoes a conformational change upon metal binding. Metal binding also enhances the tendency of the domain to dimerize. These findings suggest a model for activation of the histidine kinase through metal binding events in the periplasmic sensor domain.     

Bistable responses in bacterial genetic networks: designs and dynamical consequences

A key property of living cells is their ability to react to stimuli with specific biochemical responses. These responses can be understood through the dynamics of underlying biochemical and genetic networks. Evolutionary design principles have been well studied in networks that display graded responses, with a continuous relationship between input signal and system output. Alternatively, biochemical networks can exhibit bistable responses so that over a range of signals the network possesses two stable steady states. In this review, we discuss several conceptual examples illustrating network designs that can result in a bistable response of the biochemical network. Next, we examine manifestations of these designs in bacterial master-regulatory genetic circuits. In particular, we discuss mechanisms and dynamic consequences of bistability in three circuits: two-component systems, sigma-factor networks, and a multistep phosphorelay. Analyzing these examples allows us to expand our knowledge of evolutionary design principles networks with bistable responses.     

Characterization of Copper-Inducible Promoters Regulated by CpxA/CpxR in Escherichia coli

The copper stimulon in Escherichia coli consists of four regulons, the CueR-, CusS/CusR-, CpxA/CpxR-, and YedV/YedW regulons. E. coli mutants defective in cpxRA showed higher sensitivity to copper than the wild type. A total of 15 promoters were found to be induced in E. coli culture upon exposure to copper in a CpxA/CpxR-dependent manner. After gel-shift and DNase I foot-printing analyses, a conserved tandem repeat of pentanucleotide sequence, GTAAA(N)_4–8GTAAA, with a conserved A of 4-bp upstream of each pentamer, was identified to be the CpxR-binding site. The difference in the orientation and location of the CpxR box is discussed with respect to the regulation mechanism among CpxR-regulon genes.     

A型链球菌（GAS）毒素调控因子及其调控机制

A型链球菌是一类革兰氏阳性病原菌,其产生的多种毒素因子是导致人体多重感染的重要原因。这些菌毒素因子的表达直接或间接地受多个毒素调控系统调控,各个调控系统之间存在相互关联并对病原菌与宿主的相互作用产生影响。干扰毒素的产生或调控通路对于发展特异的抗A型链球菌感染药物具有重要的意义。     

Regulated nuclear targeting

Extracellular signals are transduced to the nucleus through respective signal transduction pathways. Evidence in animals and yeast indicates the importance of regulated nuclear targeting in these processes. Although little is known about plants in this regard, some plant signaling factors have recently been shown to translocate to the nucleus upon receipt of a signal.     

转录因子与microRNA在基因表达调控中的功能联系及差异

转录因子和微RNA(microRNA)是最大的两类反式作用因子,它们是基因表达调控的重要调控因子.它们协调发挥调控作用,精细调控基因的表达,在细胞分化和动物生长发育过程中发挥重要的作用.随着对转录因子和microRNA研究的深入,人们发现转录因子和microRNA在基因表达调控网络中关系紧密,它们的分子作用机制有许多相似之处,两者都通过各自的顺式作用元件调控基因表达,且作用的方式类似.但转录因子和microRNA也存在不同之处,转录因子既可以激活基因表达,也可抑制基因表达,而microRNA主要是抑制基因表达.另外,转录因子调控区的复杂性一般高于microRNA的调控区域.本文综述了转录因子和microRNA的异同点,并提出了未来转录因子和microRNA的研究方向.     

Signaling pathways for stress responses and adaptation in Aspergillus species: stress biology in the post-genomic era

Aspergillus species are among the most important filamentous fungi in terms of industrial use and because of their pathogenic or toxin-producing features. The genomes of several Aspergillus species have become publicly available in this decade, and genomic analyses have contributed to an integrated understanding of fungal biology. Stress responses and adaptation mechanisms have been intensively investigated using the accessible genome infrastructure. Mitogen-activated protein kinase (MAPK) cascades have been highlighted as being fundamentally important in fungal adaptation to a wide range of stress conditions. Reverse genetics analyses have uncovered the roles of MAPK pathways in osmotic stress, cell wall stress, development, secondary metabolite production, and conidia stress resistance. This review summarizes the current knowledge on the stress biology of Aspergillus species, illuminating what we have learned from the genomic data in this “post-genomic era.”     

Fungal regulatory evolution: cis and trans in the balance

Regulatory divergence is likely a major driving force in evolution. Comparative genomics is being increasingly used to infer the evolution of gene regulation. Ascomycota fungi are uniquely suited among eukaryotes for regulatory evolution studies, due to broad phylogenetic scope, many sequenced genomes, and tractability of genomic analysis. Here we review recent advances in the identification of the contribution of cis- and trans-factors to expression divergence. Whereas current strategies have led to the discovery of surprising signatures and mechanisms, we still understand very little about the adaptive role of regulatory evolution. Empirical studies including experimental evolution, comparative functional genomics and hybrid and engineered strains are showing early promise toward deciphering the contribution of regulatory divergence to adaptation.     

金黄色葡萄球菌基因调节系统研究进展

金黄色葡萄球菌是人类的一种重要病原菌,可以引起许多临床表现不同的感染性疾病。它所致感染的多样性和严重度取决于不同毒力因子的协同表达,而这些数量众多的毒力因子的表达会受到不同调节系统的控制,同时这些调节系统之间也存在着复杂的相互作用关系。这些基因调节系统主要有两大类：一类是双组分信号转导系统（如Agr、SaeRS、SrrAB、ArlSR、LytRS、WalKR）;另一类是转录因子f如Sar、Rot、MgrA、SigmaB）。它们的协同作用有助于金黄色葡萄球菌对外界环境信号做出反应,调节致病过程中毒力因子在不同情况下的表达。     

The Oligomeric Assembly of the Novel Haem-Degrading Protein HbpS Is Essential for Interaction with Its Cognate Two-Component Sensor Kinase

HbpS, a novel protein of previously unknown function from Streptomyces reticuli, is up-regulated in response to haemin- and peroxide-based oxidative stress and interacts with the SenS/SenR two-component signal transduction system. In this study, we report the high-resolution crystal structures (2.2 and 1.6 Å) of octomeric HbpS crystallized in the presence and in the absence of haem and demonstrate that iron binds to surface-exposed lysine residues of an octomeric assembly. Based on an analysis of the crystal structures, we propose that the iron atom originates from the haem group and report subsequent biochemical experiments that demonstrate that HbpS possesses haem-degrading activity in vitro. Further examination of the crystal structures has identified amino acids that are essential for assembly of the octomer. The role of these residues is confirmed by biophysical experiments. Additionally, we show that while the octomeric assembly state of HbpS is not essential for haem-degrading activity, the assembly of HbpS is required for its interaction with the cognate sensor kinase, SenS. Homologs of HbpS and SenS/SenR have been identified in a number of medically and ecologically relevant bacterial species (including Vibrio cholerae, Klebsiella pneumoniae, Corynebacterium diphtheriae, Arthrobacter aurescens and Pseudomonas putida), suggesting the existence of a previously undescribed bacterial oxidative stress-response pathway common to Gram-negative and Gram-positive bacteria. Thus, the data presented provide the first insight into the function of a novel protein family and an example of an iron-mediated interaction between an accessory protein and its cognate two-component sensor kinase.     

在ipt-GUS转基因拟南芥中双组分信号传导基因应答体内细胞分裂素的增加

ipt—GUS转录融合基因在拟南芥植物中表达,其体内细胞分裂素的含量可达到野生型的20-30倍。从拟南芥种子萌发后的6、12、20和30d四个时间分析了植物体内细胞分裂素含量的提高对其双组分信号传导系统中基因的影响。研究发现：细胞分裂素受体基因CRE1比CKI1基因更容易被增加的植物细胞分裂素诱导表达。拟南芥植物细胞分裂素反应调节基因ARR4和ARR5在植物发育的不同时期应答植物体内增加的植物细胞分裂素,ARR4的应答反应比ARR5早,种子萌发后的第6天幼苗真叶形成初期,ARR4基因被明显涛导;而ARR5的应答反应在幼苗真叶形成后的几个时间段均能检测到,并且在种子萌发后的第20天,花枝形成开始时特别明显。在双组分信号传导途径中,从受体到反应调节基因传导磷酸基团的传导基因AHP4在幼苗发育的后期种子萌发后的第20和30天,应答植物体内增加的植物细胞分裂素,并且在花枝形成初期比较明显。