Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing 100871, China.
Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14900-5. doi: 10.1073/pnas.1205241109. Epub 2012 Aug 27.
The C-terminal domain (M(pro)-C) of SARS-CoV main protease adopts two different fold topologies, a monomer and a 3D domain-swapped dimer. Here, we report that M(pro)-C can reversibly interconvert between these two topological states under physiological conditions. Although the swapped α(1)-helix is fully buried inside the protein hydrophobic core, the interconversion of M(pro)-C is carried out without the hydrophobic core being exposed to solvent. The 3D domain swapping of M(pro)-C is activated by an order-to-disorder transition of its C-terminal α(5)-helix foldon. Unfolding of this foldon promotes self-association of M(pro)-C monomers and functions to mediate the 3D domain swapping, without which M(pro)-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 α(1)-helices to swap in a hydrophobic environment, which minimizes the energy cost of the 3D domain-swapping process.
SARS-CoV 主要蛋白酶的 C 端结构域（M(pro)-C）采用两种不同的折叠拓扑结构，单体和 3D 结构域交换二聚体。在这里，我们报告 M(pro)-C 可以在生理条件下可逆地在这两种拓扑状态之间转换。尽管交换的 α(1)-螺旋完全埋在蛋白质疏水核心内，但 M(pro)-C 的转换是在疏水核心不暴露于溶剂的情况下进行的。M(pro)-C 的 3D 结构域交换是通过其 C 端 α(5)-螺旋折叠的有序到无序转变而激活的。该折叠的展开促进 M(pro)-C 单体的自组装，并起到介导 3D 结构域交换的作用，如果没有这种折叠，M(pro)-C 就不能再形成结构域交换二聚体。总之，我们提出存在一种特殊的二聚体中间态，使蛋白质核心能够解包，α(1)-螺旋在疏水环境中交换，从而使 3D 结构域交换过程的能量成本最小化。
