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首页> 外文期刊>Biochemistry >Interaction of a peptide from the receptor-binding domain of Pseudomonas aeruginosa pili strain PAK with a cross-reactive antibody: changes in backbone dynamics induced by binding.
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Interaction of a peptide from the receptor-binding domain of Pseudomonas aeruginosa pili strain PAK with a cross-reactive antibody: changes in backbone dynamics induced by binding.

机译：铜绿假单胞菌菌毛菌PAK的受体结合域中的肽与交叉反应抗体的相互作用：结合诱导的骨架动力学变化。

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摘要

The C-terminal receptor-binding region of Pseudomonas aeruginosa pilin protein strain PAK (residues 128-144) has been the target for the design of a vaccine effective against P. aeruginosa infections. We have recently cloned and expressed a (15)N-labeled PAK pilin peptide spanning residues 128-144 of the PAK pilin protein. The peptide exists as a major (trans) and minor (cis) species in solution, arising from isomerization around a central Ile(138)-Pro(139) peptide bond. The trans isomer adopts two well-defined turns in solution, a type I beta-turn spanning Asp(134)-Glu-Gln-Phe(137) and a type II beta-turn spanning Pro(139)-Lys-Gly-Cys(142). The cis isomer adopts only one well-defined type II beta-turn spanning Pro(139)-Lys-Gly-Cys(142) but displays evidence of a less ordered turn spanning Asp(132)-Gln-Asp-Glu(135). These turns have been implicated in cross-reactive antibody recognition. (15)N NMR relaxation experiments of the (15)N-labeled recombinant PAK pilin peptide in complex with an Fab fragment of a cross-reactive monoclonal antibody, PAK-13, raised against the intact PAK pilus, were performed in order to probe for changes in the mobilities and dynamics of the peptide backbone as a result of antibody binding. The major results of these studies are as follows: binding of Fab leads to the preferential ordering of the first turn over the second turn in each isomer, binding of Fab partially stabilizes peptide backbone regions undergoing slow (microsecond to millisecond) exchange-related motions, and binding of Fab leads to a greater loss in backbone conformational entropy at pH 7.2 versus pH 4.5. The biological implications of these results will be discussed in relation to the role that fast and slow backbone motions play in PAK pilin peptide immunogenicity and within the framework of developing a pilin peptide vaccine capable of conferring broad immunity across P. aeruginosa strains.
机译：铜绿假单胞菌菌毛蛋白蛋白菌株PAK（残基128-144）的C末端受体结合区已成为设计有效对抗铜绿假单胞菌感染的疫苗的目标。我们最近克隆并表达了跨越PAK菌毛蛋白128-144位残基的（15）N标记的PAK菌毛蛋白肽。由于围绕中心Ile（138）-Pro（139）肽键的异构化作用，该肽在溶液中以主要（反式）和次要（顺式）形式存在。反式异构体在溶液中采用两个明确定义的转角，一个I型β转角跨越Asp（134）-Glu-Gln-Phe（137）和II型β转角跨越Pro（139）-Lys-Gly-Cys （142）。顺式异构体仅采用一种定义明确的II型β跨度跨度Pro（139）-Lys-Gly-Cys（142），但显示跨度较小的跨度跨度为Asp（132）-Gln-Asp-Glu（135）的证据。这些转折与交叉反应性抗体识别有关。 （15）N标记的重组PAK菌毛蛋白肽与针对完整PAK菌毛的交叉反应性单克隆抗体PAK-13的Fab片段复合的（15）N NMR弛豫实验，以进行探测抗体结合导致肽主链的迁移率和动力学变化的结果。这些研究的主要结果如下：Fab的结合导致每个异构体中第一回合优先于第二回合的优先顺序，Fab的结合部分稳定了经历缓慢（微秒至毫秒）交换相关运动的肽骨架区域， Fab的结合导致pH 7.2和pH 4.5时骨架构象熵的损失更大。将讨论这些结果的生物学意义，涉及快慢骨架在PAK毛蛋白肽免疫原性中的作用，以及在开发能够对铜绿假单胞菌菌株赋予广泛免疫力的毛蛋白肽疫苗的框架内。

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