Weak oligomerization of low-molecular-weight protein tyrosine phosphatase is conserved from mammals to bacteria
Weak oligomerization of low-molecular-weight protein tyrosine phosphatase is conserved from mammals to bacteria
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DOI：
10.1111/j.1742-4658.2009.07139.x
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发表时间：
2009-08-01
期刊：
影响因子：
5.4
通讯作者：
Pons, Miquel
中科院分区：
文献类型：
--
作者：
Blobel, Jascha;Bernado, Pau;Pons, Miquel
哺乳动物低分子量蛋白酪氨酸磷酸酶（lmwPTP）的良好表征的自缔合产生与活性单体平衡的非活性寡聚体。已经提出了作为超分子酶原的无活性寡聚体的作用。用核磁共振法研究了枯草芽孢杆菌（Bacillus subtilis）的一种lmwPTP（Yw1E）的低聚平衡。化学位移数据和NMR弛豫证实，二聚化发生通过酶的活性位点，是完全等同于二聚化以前的特点是在一个真核低分子量磷酸酶，具有类似的大解离常数。原核和真核磷酸酶的寡聚化之间的相似性超出了二聚体，并涉及在高蛋白浓度下通过NMR弛豫分析检测到的高阶寡聚体。在不同的生命王国的保护表明，尽管在体外观察到的弱关联的lmwPTP寡聚化的生理作用。结构数据表明，底物调节的寡聚化平衡可能是一种调节机制，导致产生的信号脉冲。在Yw1E的二聚化位点中存在苯丙氨酸残基，取代了所有真核lmwPTP中保守的酪氨酸残基，表明通过寡聚化的lmwPTP调节可以独立于酪氨酸磷酸化。
The well-characterized self-association of a mammalian low-molecular-weight protein tyrosine phosphatase (lmwPTP) produces inactive oligomers that are in equilibrium with active monomers. A role of the inactive oligomers as supramolecular proenzymes has been suggested. The oligomerization equilibrium of Yw1E, a lmwPTP from Bacillus subtilis, was studied by NMR. Chemical shift data and NMR relaxation confirm that dimerization takes place through the enzyme's active site, and is fully equivalent to the dimerization previously characterized in a eukaryotic low-molecular-weight phosphatase, with similarly large dissociation constants. The similarity between the oligomerization of prokaryotic and eukaryotic phosphatases extends beyond the dimer and involves higher order oligomers detected by NMR relaxation analysis at high protein concentrations. The conservation across different kingdoms of life suggests a physiological role for lmwPTP oligomerization in spite of the weak association observed in vitro. Structural data suggest that substrate modulation of the oligomerization equilibrium could be a regulatory mechanism leading to the generation of signaling pulses. The presence of a phenylalanine residue in the dimerization site of Yw1E, replacing a tyrosine residue conserved in all eukaryotic lmwPTPs, demonstrates that lmwPTP regulation by oligomerization can be independent from tyrosine phosphorylation.