A hydrophobic patch in the competence-stimulating peptide, a pneumococcal competence pheromone, is essential for specificity and biological activity
A hydrophobic patch in the competence-stimulating peptide, a pneumococcal competence pheromone, is essential for specificity and biological activity
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DOI：
10.1128/jb.188.5.1744-1749.2006
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Håvarstein, LS
中科院分区：
文献类型：
--
作者：
Johnsborg, O;Kristiansen, PE;Håvarstein, LS
肺炎链球菌天然遗传转化的诱导能力依赖于信息素介导的细胞间通讯和由能力刺激肽（CSP）、其膜嵌入的组氨酸激酶受体ComD和同源反应调节因子ComE组成的信号传导途径。对肺炎球菌分离株的广泛筛选显示，在该物种的成员中发现了两种主要的CSP变体，CSP 1和CSP 2。尽管CSP 1和CSP 2的一级结构约有50%相同，但它们对其各自的受体ComD 1和ComD 2具有高度特异性。在目前的工作中，我们已经调查了这种特异性的结构基础，通过确定的三维结构的CSP 1的核磁共振数据和比较的激动剂活性的CSP 1/CSP 2的混合肽的数量对ComD 1和ComD 2受体。我们的研究结果表明，在暴露于膜模拟环境中，17个氨基酸的CSP 1信息素采用两亲性α-螺旋构型从残基6延伸到残基12。此外，由各种杂合肽显示的激动剂活性的模式显示，疏水性氨基酸，其中一些位于α-螺旋的非极性侧，强烈地有助于CSP特异性。总之，这些数据表明，所鉴定的α-螺旋是CSP 1的重要结构特征，其对于在自然条件下的有效受体识别是必不可少的。
Induction competence for natural genetic transformation in Streptococcus pneumoniae depends on pheromone-mediated cell-cell communication and a signaling pathway consisting of the competence-stimulating peptide (CSP), its membrane-embedded histidine kinase receptor ComD, and the cognate response regulator ComE. Extensive screening of pneumococcal isolates has revealed that two major CSP variants, CSP1 and CSP2, are found in members of this species. Even though the primary structures of CSP1 and CSP2 are about 50% identical, they are highly specific for their respective receptors, ComD1 and ComD2. In the present work, we have investigated the structural basis of this specificity by determining the three-dimensional structure of CSP1 from nuclear magnetic resonance data and comparing the agonist activity of a number of CSP1/CSP2 hybrid peptides toward the ComD1 and ComD2 receptors. Our results show that upon exposure to membrane-mimicking environments, the 17-amino-acid CSP1 pheromone adopts an amphiphilic alpha-helical configuration stretching from residue 6 to residue 12. Furthermore, the pattern of agonist activity displayed by the various hybrid peptides revealed that hydrophobic amino acids, some of which are situated on the nonpolar side of the alpha-helix, strongly contribute to CSP specificity. Together, these data indicate that the identified alpha-helix is an important structural feature of CSP1 which is essential for effective receptor recognition under natural conditions.