Structural basis of acyl-homoserine lactone-dependent signaling.

Structural basis of acyl-homoserine lactone-dependent signaling.
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DOI:
10.1021/cr1000817
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发表时间:
2011-01-12
期刊:
影响因子:
62.1
通讯作者:
Chen, Lingling
Chen, Lingling
中科院分区:
化学1区
文献类型:
--
作者:
Churchill, Mair E. A.;Chen, Lingling

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酰基高丝氨酸内酯是小的中性脂质分子,变形菌门中的细菌用它来感知和发出细胞密度信号。这种信号传导过程被称为群体感应,可激活细菌群体内向不同社区导向的生活方式的分化。自从 40 年前首次描述自感应1和产光革兰氏阴性菌费氏弧菌 (Vibrio fischeri) 2, 3(夏威夷短尾鱿鱼 Euprymna scolopes 的共生体)中的群体感应系统以来,人们对这些细菌和许多相关细菌中信号传导的分子机制有了很多了解(参考文献 4 和参考文献 5 中的第 5-25 章进行了综述)。革兰氏阴性细菌用于感知细胞密度的主要信号是酰基高丝氨酸内酯 (AHL) 分子,该分子由高丝氨酸内酯环 (HSL) 和酰基链组成(图 1)。酰基链长度通常从C4到C18、6、7变化,并且可以通过3-氧取代基或在某些情况下通过3-羟基取代基、末端甲基支链或不同的不饱和度来修饰。 8 AHL 由称为 AHL 合酶的酶合成。 7, 9 一旦产生,AHL 就会通过被动 10 和主动运输机制扩散进出细胞。 11 AHL 的浓度最终在给定的细胞数量或细菌“群体”阈值下达到足够高的浓度,然后被受体蛋白(系统的第二个组成部分)识别。 AHL 响应受体包括多种称为“R 蛋白”的转录调节因子,例如 LuxR 或 LasR,它们是 DNA 结合转录因子 4、12 以及与 LuxN 相关的一小类传感器激酶。 13 大多数特征性 R 蛋白与 AHL 的结合会启动靶基因的激活和抑制,在某些情况下,AHL 结合会导致靶基因去抑制。 14-18 本综述的重点是革兰氏阴性细菌中 AHL 信号介导的群体感应的结构基础(参见参考文献 19-21)。这些结构数据
Acyl-homoserine lactones are small neutral lipid molecules that bacteria in the Proteobacteria group use to sense and signal their cell density. This signaling process, known as quorum sensing, activates differentiation to diverse community-oriented lifestyles within the bacterial population. Since the first description of autoinduction 40 years ago1 and quorum sensing systems in the light-producing Gramnegative bacterium Vibrio fischeri, 2, 3 which is a symbiont of the Hawaiian bobtail squid Euprymna scolopes, much has been learned about the molecular mechanism of signaling in these and many related bacteria (reviewed in ref 4 andChapters 5-25 in ref 5). The primary signals used by Gramnegative bacteria to sense cell density are acyl-homoserine lactone (AHL) molecules, which are composed of a homoserine lactone ring (HSL) with an acyl chain (Figure 1). The acyl chain length generally varies from C4 to C18, 6, 7 and this can be modified by a 3-oxo substituent or, in some cases, a 3-hydroxy substituent, a terminal methyl branch, or varied degrees of unsaturation. 8 AHLs are synthesized by enzymes known as the AHL synthases. 7, 9 Once produced, the AHLs diffuse in and out of the cell by passive10 as well as active transport mechanisms. 11 The concentration of AHL eventually reaches a sufficiently high concentration at a given threshold cell number or bacterial “quorum”, and it is then recognized by a receptor protein, which is the second component of the system. The AHL-responsive receptors include a wide variety of transcriptional regulators called “R proteins”, such as LuxR or LasR, which are DNA-binding transcription factors, 4, 12 and a small family of sensor kinases related to LuxN. 13 The binding of the AHL by most of the characterized R-proteins initiates the activation and repression of target genes, and in some cases, AHL binding leads to target gene derepression. 14-18 The focus of this review is the structural basis for quorum sensing mediated by AHL signals in Gram-negative bacteria (reviewed in refs 19-21). The structural data in these
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