A conserved residue at the extreme C-terminus of FtsZ is critical for the FtsA-FtsZ interaction in Staphylococcus aureus.

A conserved residue at the extreme C-terminus of FtsZ is critical for the FtsA-FtsZ interaction in Staphylococcus aureus.
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FtsZ C 末端的保守残基对于金黄色葡萄球菌中的 FtsA-FtsZ 相互作用至关重要。

DOI:
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发表时间:
2000
期刊:
Biochemical and Biophysical Research Communications - BBRC
影响因子:
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通讯作者:
David J. Payne
David J. Payne
中科院分区:
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文献类型:
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作者:
Kang Yan;Kenneth H. Pearce;David J. Payne

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FtsZ是一种具有GTP酶活性的微管蛋白样蛋白,FtsA是一种具有ATP酶活性的肌动蛋白样蛋白,已知这两种蛋白质在细菌细胞周期的后期发挥关键作用。FtsA-FtsZ共定位于分裂细菌的隔膜处对于E.杆菌我们已经通过共表达FtsA和FtsZ验证和表征了这种相互作用,FtsA和FtsZ来自E. coli和革兰氏阳性菌S.在酵母双杂交系统中,金黄色葡萄球菌。我们首次证明了S.金黄色葡萄球菌FtsA和FtsZ蛋白及其自身相互作用。金黄色葡萄球菌FtsZ这些观察结果与FtsA和FtsZ在细菌细胞分裂中的保守作用一致。通过缺失突变,我们发现在S.金黄色葡萄球菌FtsZ在与FtsA的相互作用中是关键的。通过丙氨酸扫描诱变对该基序的进一步分析显示Phe 376可能在FtsA-FtsZ相互作用中起主要作用。该研究对设计FtsA-FtsZ相互作用的拮抗剂和激动剂具有重要意义,因为此类试剂可提供一种处理多重耐药革兰氏阳性病原体的新方法。
FtsZ, a tubulin-like protein with GTPase activity, and FtsA, an actin-like protein with ATPase activity, are two proteins known to play critical roles in the later stages of the bacterial cell cycle. It is well documented that FtsA-FtsZ co-localization at the septum of dividing bacteria is essential for successful cell division in E. coli. We have validated and characterized this interaction by co-expressing FtsA and FtsZ, from both E. coli and S. aureus, in the yeast two-hybrid system. We demonstrate for the first time a specific association between S. aureus FtsA and FtsZ proteins and self interaction of S. aureus FtsZ. These observations are consistent with the conserved role of FtsA and FtsZ in bacterial cell division. Using deletion mutagenesis, we have shown that a highly conserved motif as small as 10 residues in the extreme C-terminus of S. aureus FtsZ is critical for the interaction with FtsA. Further dissection of this motif by alanine scanning mutagenesis showed that Phe376 likely plays a major role in the FtsA-FtsZ interaction. This work has important implications for the design of antagonists and agonists of the FtsA-FtsZ interaction as such agents could provide a novel approach for tackling multi-resistant Gram positive pathogens.