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克雷白氏肺炎桿菌中調控莢膜多醣體生合成之調節蛋白RcsB結構與功能之特性分析
Thesis

克雷白氏肺炎桿菌中調控莢膜多醣體生合成之調節蛋白RcsB結構與功能之特性分析

Lee, Chien-Yun
Masters, 國立清華大學, 生物資訊與結構生物研究所
2010

Abstract

克雷白氏肺炎桿菌 莢膜多醣體 RcsB Klebsiella pneumoniae capsular polysaccharide
Klebsiella pneumoniae, an important pathogen of hospital infections, necessarily produces plenty of capsular polysaccharide (CPS) to prevent phagocytosis from the hosts. The response regulator RcsB is essential for regulating CPS prodution but its regulatory mechanism remains unclear. Here, we cloned wild-type RcsB to characterize the structural and functional properties. To clarify the effect of phosphorylation in RcsB, a constitutive mutant D56E was also constructed. Electrophoretic mobility shift assay reveals that D56E apparently enhanced its binding ability with cps gene promoter, indicating phosphorylation might raise expression level of cps genes. Moreover, our biophysical studies demonstrate that D56E not only triggers formation of tetramer via charge-charge interactions but also enhances thermal stability, which is not found in wild-type RcsB. According to our bioinformatic analysis, N-terminal phosphoreceiver domain plays an important role in oligomerization. Our results show that N-terminal domain exhibits similar biophysical properties with that of full-length RcsB. Interestingly, N-terminal domain of D56E has a quite different HSQC spectrum as compared with that of wild-type RcsB, implying conformation is moderately changed upon phosphorylation. Hence we proposed that the N-terminal domain has to be phosphorylated to alter its structure, thus triggering the formation of oligomers. This oligomer is critical for promoting DNA-binding in regulation of CPS production.

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