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首页> 外文期刊>The FEBS journal >Biochemical characterization of the tandem HAMP domain from Natronomonas pharaonis as an intraprotein signal transducer
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Biochemical characterization of the tandem HAMP domain from Natronomonas pharaonis as an intraprotein signal transducer

机译：法老氏单胞菌的串联HAMP结构域作为蛋白内信号转导子的生化特性

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摘要

Available structures of HAMP domains suggest rotation as one potential mechanism in intraprotein signal transduction. It has been proposed that in poly-HAMP modules the signal sign is inverted with each additional HAMP. We examined signal transduction through the HAMP tandem domain from the phototaxis transducer of the halophilic archaeon Natronomonas pharaonis in membrane-bound chimeras consisting of the Escherichia coli chemotaxis receptor for serine, Tsr, as an input and the mycobacterial adenylyl cyclase Rv3645 as an output domain, i.e. the basic chimera was 'Tsr-NpHAMP tandem-Rv3645 cyclase'. Neither of the NpHAMP units alone nor the NpHAMP tandem transduced a serine signal. After five targeted point mutations in the first alpha-helix of NpHAMP(1), the non-functional NpHAMP modules combined into a functional HAMP tandem. 1 mM serine significantly inhibited cyclase activity (-35%; IC50 = 30 mu M) in disagreement with the structure-based predictions. Surprisingly, replacement of NpAS1(1) in the tandem by the respective AS1 from HAMP(Tsr) resulted in signal inversion, i.e. serine activated cyclase (+129%; EC50 = 10 mu M). Examination of 48 mutants of AS1(1) in the HAMP tandem including two residues of a putative N-terminal control cable identified five residues in NpAS1(1) which probably define different ground states of the output domain and thus affect the sign of signal output. The data question the predicted HAMP rotation as the predominant mechanism of intraprotein signal transduction and point to as yet unrecognized conformational motions of HAMP domains in intraprotein signaling.
机译：HAMP域的可用结构表明旋转是蛋白内信号转导的一种潜在机制。已经提出，在多HAMP模块中，信号符号与每个附加的HAMP相反。我们研究了由膜结合的嵌合体中的嗜盐古细菌Natronomonas pharaonis的趋光性传感器通过HAMP串联域进行的信号转导，该膜结合的嵌合体由大肠杆菌的趋化性受体丝氨酸Tsr作为输入，而分枝杆菌腺苷酸环化酶Rv3645作为输出域，即基本嵌合体是“ Tsr-NpHAMP串联-Rv3645环化酶”。 NpHAMP单元和NpHAMP串联均不能转导丝氨酸信号。在NpHAMP（1）的第一个alpha螺旋中有五个目标点突变后，非功能性NpHAMP模块组合为功能性HAMP串联。 1 mM丝氨酸明显抑制环化酶活性（-35％; IC50 = 30μM），与基于结构的预测不一致。令人惊讶的是，由来自HAMP（Tsr）的相应AS1串联替换NpAS1（1）导致信号反转，即丝氨酸激活的环化酶（+ 129％; EC 50 ＝10μM）。检查HAMP串联中的AS1（1）的4​​8个突变体，包括一个假定的N端控制电缆的两个残基，确定了NpAS1（1）中的五个残基，它们可能定义了输出域的不同基态，从而影响信号输出的符号。数据质疑了预测的HAMP旋转是蛋白内信号转导的主要机制，并指出了蛋白内信号中HAMP域的尚未被认识的构象运动。

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