title: Foldon unfolding mediates the interconversion between M(pro)-C monomer and 3D domain-swapped dimer.
abstract: 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.
authors.affiliation: Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing 100871, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Kang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhong
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhang
authors.forename: Changwen
authors.initials: C
authors.lastname: Jin
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
mesh_terms: D002942:Circular Dichroism; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics*; D019281:Dimerization; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D013113:Spin Labels; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D013113:Spin Labels; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases