Foldon unfolding mediates the interconversion between Mpro-C monomer and 3D domain-swapped dimer
Foldon unfolding mediates the interconversion between Mpro-C monomer and 3D domain-swapped dimer
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Foldon 解折叠介导 Mpro-C 单体和 3D 结构域交换二聚体之间的相互转化
DOI：
10.1073/pnas.1205241109
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发表时间：
2012-09-11
影响因子：
11.1
通讯作者：
Xia, Bin
中科院分区：
文献类型：
--
作者：
Kang, Xue;Zhong, Nan;Xia, Bin
SARS-CoV主酶C末端结构域(MPRO-C)采用两种不同的折叠拓扑结构，即单体和3D结构域交换的二聚体。在这里，我们报道了在生理条件下，MPRO-C可以在这两种拓扑态之间进行可逆的相互转换。虽然交换的MPRO 1-螺旋完全埋在蛋白质疏水核心内，但α-C的相互转化是在疏水核心不暴露于溶剂的情况下进行的。Mpro-C的3D结构域交换是由其C-末端α5-螺旋折叠的有序到无序转变激活的。这一折叠的展开促进了MPRO-C单体的自缔合，并发挥了介导3D结构域交换的功能，如果没有这种功能，MPRO-C就不能再形成结构域交换的二聚体。综上所述，我们认为存在一种特殊的二聚体中间体，使蛋白质核心能够在疏水环境中解包和α1-螺旋交换，从而最小化3D结构域交换过程的能量成本。
The C-terminal domain (Mpro-C) of SARS-CoV main protease adopts two different fold topologies, a monomer and a 3D domain-swapped dimer. Here, we report that Mpro-C can reversibly interconvert between these two topological states under physiological conditions. Although the swapped α1-helix is fully buried inside the protein hydrophobic core, the interconversion of Mpro-C is carried out without the hydrophobic core being exposed to solvent. The 3D domain swapping of Mpro-C is activated by an order-to-disorder transition of its C-terminal α5-helix foldon. Unfolding of this foldon promotes self-association of Mpro-C monomers and functions to mediate the 3D domain swapping, without which Mpro-C can no longer form the domain-swapped dimer. Taken together, we propose that there exists a special dimeric intermediate enabling the protein core to unpack and the α1-helices to swap in a hydrophobic environment, which minimizes the energy cost of the 3D domain-swapping process.