Allosteric signal transmission involves synergy between discrete structural units of the regulatory subunit of aspartate transcarbamoylase.
Allosteric signal transmission involves synergy between discrete structural units of the regulatory subunit of aspartate transcarbamoylase.
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变构信号传递涉及天冬氨酸转氨甲酰酶调节亚基的离散结构单元之间的协同作用。
DOI：
10.1006/abbi.1999.1570
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发表时间：
2000
影响因子：
3.9
通讯作者：
Wild,JR
中科院分区：
文献类型：
--
作者：
Liu,L;Wales,ME;Wild,JR
以往的研究表明粘质沙雷氏菌和大肠杆菌天冬氨酸氨基转移酶(ATCase)调节多肽的S5‘β链(r93-r97)负责它们不同的变构调节模式，包括将粘质沙雷氏菌中的CTP从抑制因子转化为粘质沙雷氏菌中的激活剂。同样，位于变构结构域和锌结构域之间的残基的突变导致了大肠杆菌酶的ATP反应从激活转变为抑制，这表明该界面不仅介导并区分了ATP和CTP的变构反应。为了进一步了解这些区域在变构通讯中的作用和相互关系，变构-锌界面突变(Y77F和V106A)被引入到天然和S5‘β-链嵌合背景中。虽然这个界面在变构调节中的重要性已经得到证实，但没有直接证据支持通过这个界面存在不同的ATP和CTP信号通路。对所报道的突变效应的分析表明，S5‘β链通过调节疏水的变构-锌界面而不是干扰变构配体的结合来传递变构信号。通过在变构和调控链锌结构域之间的疏水界面上的替换来抑制基因内的替换，导致EC：RS5‘sm嵌合体中变构反应的部分恢复，并降低了Sm：RS5’EC嵌合体中ATP的激活。因此，这两个结构单元之间似乎存在协同效应。
Previous studies have shown that the S5′ β-strand (r93–r97) of the regulatory polypeptides of the aspartate transcarbamoylases (ATCases) from Serratia marcescens and Escherichia coli are responsible for their diverged allosteric regulatory patterns, including conversion of CTP from an inhibitor in E. coli to an activator in S. marcescens. Similarly, mutation of residues located in the interface between the allosteric and the zinc domains resulted in conversion of the ATP responses of the E. coli enzyme from activation to inhibition, suggesting that this interface not only mediates but also discriminates the allosteric responses of ATP and CTP. To further decipher the roles and the interrelationships of these regions in allosteric communication, allosteric–zinc interface mutations (Y77F and V106A) have been introduced into both the native and the S5′ β-strand chimeric backgrounds. While the significance of this interface in the allosteric regulation has been confirmed, there is no direct evidence supporting the presence of distinct pathways for the ATP and CTP signals through this interface. The analysis of the mutational effects reported here suggested that the S5′ β-strand transmits the allosteric signal by modulating the hydrophobic allosteric–zinc interface rather than disturbing the allosteric ligand binding. Intragenic suppression by substitutions in the hydrophobic interface between the allosteric and the zinc domains of the regulatory chains resulted in the partial recovery of allosteric responses in the EC:rS5′sm chimera and reduced the activation by ATP in the Sm:rS5′ec chimera. Thus, it seems that there is a synergy between these two structural units.