Identification of Ligand Specificity Determinants in Lantibiotic Bovicin HJ50 and the Receptor BovK, a Multitransmembrane Histidine Kinase*
Identification of Ligand Specificity Determinants in Lantibiotic Bovicin HJ50 and the Receptor BovK, a Multitransmembrane Histidine Kinase*
复制标题
羊毛硫抗生素 Bovicin HJ50 和受体 BovK（一种多跨膜组氨酸激酶）中配体特异性决定因素的鉴定*
DOI：
10.1074/jbc.m113.513150
复制
发表时间：
2014-02
影响因子：
4.8
通讯作者：
Zhong, Jin
中科院分区：
文献类型：
--
作者：
Gao, Yong;Wang, Jian;Lin, Yuheng;Zhong, Jin
背景：许多羊毛硫抗生素肽通过组氨酸激酶受体诱导其自身的生物合成。结果：Bovicin HJ 50和BovK形成信号复合物;每个蛋白质中关键氨基酸的取代导致信号传导中断。结论：Bovicin HJ 50通过疏水和静电相互作用激活BovK启动信号转导。意义：发现了一种激活多跨膜组氨酸激酶机制的新肽。牛羊毛硫抗生素（Lantibiotic bovicin）HJ 50是由牛链球菌（Streptococcus bovis）HJ 50产生的，通过BovK/R双组分系统作为胞外信号自动调节自身的生物合成。Bovicin HJ 50显示线性N-末端和glubolar C-末端结构，并且传感器组氨酸激酶BovK包含八个跨膜片段，缺乏任何广泛的表面暴露的感觉结构域。Bovicin HJ 50和BovK之间的信号识别机制尚不清楚。我们进行了饱和丙氨酸扫描诱变和其他氨基酸取代的bovicin HJ 50使用半体外生物合成。突变体诱导活性的结果表明，Bovicin HJ 50的B环上的几个带电荷的疏水氨基酸以及两个甘氨酸是识别BovK的关键残基。圆二色谱分析表明，这两个甘氨酸的bovicin HJ 50的膜结构的变化。生物素标记的bovicin HJ 50可以与BovK的N端传感器相互作用，并且BovK传感器结构域的N端部分中的几个带电残基和保守的疏水区域对于与信号bovicin HJ 50相互作用是重要的。结合以上结果，我们推测Bovicin HJ 50主要通过静电相互作用和疏水相互作用识别和激活BovK。
Background: Many lantibiotic peptides induce their own biosynthesis through histidine kinase receptors. Results: Bovicin HJ50 and BovK form a signaling complex; substitutions of key amino acids in each protein result in disrupted signal transduction. Conclusion: Bovicin HJ50 activates BovK through hydrophobic and electrostatic interaction to start signal transduction. Significance: A novel peptide activating multitransmembrane histidine kinase mechanism was identified. Lantibiotic bovicin HJ50 is produced by Streptococcus bovis HJ50 and acts as the extracellular signal to autoregulate its own biosynthesis through BovK/R two-component system. Bovicin HJ50 shows a linear N-terminal and glubolar C-terminal structure, and the sensor histidine kinase BovK contains eight transmembrane segments lacking any extensive surface-exposed sensory domain. The signal recognition mechanism between bovicin HJ50 and BovK is still unknown. We performed saturated alanine scanning mutagenesis and other amino acid substitutions on bovicin HJ50 using a semi-in vitro biosynthesis. Results of the mutants inducing activities indicated that several charged and hydrophobic amino acids in ring B of bovicin HJ50, as well as two glycines were key residues to recognize BovK. Circular dichroism analyses indicated that both glycines contributed to bovicin HJ50 structural changes in the membrane. Biotin-labeled bovicin HJ50 could interact with the N-terminal sensor of BovK, and several charged residues and a conserved hydrophobic region in the N-terminal portion of BovK sensor domain were important for interacting with the signal bovicin HJ50. By combining the results, we suggested a mechanism of bovicin HJ50 recognizing and activating BovK mainly through electrostatic and hydrophobic interactions.
登录
查看更多内容
影响因子：
62.1
作者：
Thoendel, Matthew;Kavanaugh, Jeffrey S.;Flack, Caralyn E.;Horswill, Alexander R.
通讯作者：
Horswill, Alexander R.
影响因子：
4.4
作者：
Jianqiang Ni;Kunling Teng;Gang Liu;C. Qiao;Liandong Huan;Jin Zhong
通讯作者：
Jianqiang Ni;Kunling Teng;Gang Liu;C. Qiao;Liandong Huan;Jin Zhong
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
K. Livak;Thomas D. Schmittgen
通讯作者：
K. Livak;Thomas D. Schmittgen
影响因子：
3.2
作者：
Johnsborg, O;Diep, DB;Nes, IF
通讯作者：
Nes, IF
影响因子：
1.5
作者：
Haijie Xiao;Xiuzhu Chen;Meiling Chen;Shan Tang;Xin Zhao;Liandong Huan
通讯作者：
Haijie Xiao;Xiuzhu Chen;Meiling Chen;Shan Tang;Xin Zhao;Liandong Huan