How metal cofactors drive dimer?dodecamer transition of the M42 aminopeptidase TmPep1050 of Thermotoga maritima
How metal cofactors drive dimer?dodecamer transition of the M42 aminopeptidase TmPep1050 of Thermotoga maritima
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DOI：
10.1074/jbc.ra119.009281
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发表时间：
2019-11-22
影响因子：
4.8
通讯作者：
Droogmans, Louis
中科院分区：
文献类型：
--
作者：
Dutoit, Raphael;Van Gompel, Tom;Droogmans, Louis
M42氨肽酶是一种具有12个亚基的独特四面体结构的双核氨肽酶。它们的四级结构是由它们的二价金属离子辅因子控制的六个二聚体的自组装产生的。寡聚状态的过渡仍然存在争议，尽管几个古细菌M42氨基肽酶的结构特征。主要的瓶颈是缺乏二聚体结构，阻碍了对低聚过程中发生的结构变化的理解。我们提出的第一个二聚体结构的M42氨肽酶，TmPep1050的海栖热袍菌，沿着的十二聚体结构。这两种结构的比较使我们能够描述金属离子辅因子如何调节活性位点折叠，随后，影响二聚体之间的相互作用界面。突变研究表明，M1位点严格控制十二聚体的形成。TmPep1050的十二聚体结构还揭示了二聚化结构域的一部分界定了催化口袋，并可能参与底物结合。
The M42 aminopeptidases are dinuclear aminopeptidases displaying a peculiar tetrahedron-shaped structure with 12 subunits. Their quaternary structure results from the self-assembly of six dimers controlled by their divalent metal ion cofactors. The oligomeric-state transition remains debated despite the structural characterization of several archaeal M42 aminopeptidases. The main bottleneck is the lack of dimer structures, hindering the understanding of structural changes occurring during the oligomerization process. We present the first dimer structure of an M42 aminopeptidase, TmPep1050 of Thermotoga maritima, along with the dodecamer structure. The comparison of both structures has allowed us to describe how the metal ion cofactors modulate the active-site fold and, subsequently, affect the interaction interface between dimers. A mutational study shows that the M1 site strictly controls dodecamer formation. The dodecamer structure of TmPep1050 also reveals that a part of the dimerization domain delimits the catalytic pocket and could participate in substrate binding.