Phosphorylation-independent activity of atypical response regulators of Helicobacter pylori
Phosphorylation-independent activity of atypical response regulators of Helicobacter pylori
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DOI：
10.1128/jb.187.9.3100-3109.2005
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发表时间：
2005-05-01
影响因子：
3.2
通讯作者：
Beier, D
中科院分区：
文献类型：
--
作者：
Schär, J;Sickmann, A;Beier, D
胃病原体幽门螺杆菌的基因组含有数量非常少的调节基因，包括分别编码二组分组氨酸激酶和反应调节器的三个和五个开放阅读框，这些基因被认为参与转录调节。两个反应调节基因 hp1043 和 hp166 被证明对细胞生长至关重要，而反应调节基因 hp1021 失活会导致严重的生长缺陷，如小集落表型所示。反应调节剂HP1043和HP1021的受体结构域的序列与受体结构域的酸性袋的共有序列不同，该受体结构域参与从组氨酸激酶到反应调节剂的磷酸转移反应。使用遗传互补系统，我们证明了细胞生长所必需的反应调节因子 HP166 的功能可以通过在磷酸化位点携带 D52N 取代的突变衍生物来提供。我们发现 HP1043 和 HP1021 的非典型接收序列对于这些响应调节器的功能并不重要。 HP1043 和 HP1021 受体结构域的磷酸化对于响应调节器功能来说不是必需的，并且可能根本不会发生。因此，这些调节剂的磷酸化独立作用不同于成熟的双组分范例。
The genome of the gastric pathogen Helicobacter pylori harbors a remarkably low number of regulatory genes, including three and five open reading frames encoding two-component histidine kinases and response regulators, respectively, which are putatively involved in transcriptional regulation. Two of the response regulator genes, hp1043 and hp166, proved to be essential for cell growth, and inactivation of the response regulator gene hp1021 resulted in a severe growth defect, as indicated by a small-colony phenotype. The sequences of the receiver domains of response regulators HP1043 and HP1021 differ from the consensus sequence of the acidic pocket of the receiver domain which is involved in the phosphotransfer reaction from the histidine kinase to the response regulator. Using a genetic complementation system, we demonstrated that the function of response regulator HP166, which is essential for cell growth, can be provided by a mutated derivative carrying a D52N substitution at the site of phosphorylation. We found that the atypical receiver sequences of HP1043 and HP1021 are not crucial for the function of these response regulators. Phosphorylation of the receiver domains of HP1043 and HP1021 is not needed for response regulator function and may not occur at all. Thus, the phosphorylation-independent action of these regulators differs from the well-established two-component paradigm.