C‐terminal domain of SARS‐CoV main protease can form a 3D domain‐swapped dimer

N Zhong, S Zhang, F Xue, X Kang, P Zou… - Protein …, 2009 - Wiley Online Library
N Zhong, S Zhang, F Xue, X Kang, P Zou, J Chen, C Liang, Z Rao, C Jin, Z Lou, B Xia
Protein Science, 2009Wiley Online Library
SARS coronavirus main protease (Mpro) plays an essential role in the extensive proteolytic
processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-
SARS drug development. We have reported that both the Mpro C-terminal domain alone
(Mpro-C) and the N-finger deletion mutant of Mpro (Mpro-D7) exist as a stable dimer and a
stable monomer (Zhong et al., J Virol 2008; 82: 4227-4234). Here, we report structures of
both Mpro-C monomer and dimer. The structure of the Mpro-C monomer is almost identical …
Abstract
SARS coronavirus main protease (Mpro) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. We have reported that both the Mpro C-terminal domain alone (Mpro-C) and the N-finger deletion mutant of Mpro (Mpro-D7) exist as a stable dimer and a stable monomer (Zhong et al., J Virol 2008; 82: 4227-4234). Here, we report structures of both Mpro-C monomer and dimer. The structure of the Mpro-C monomer is almost identical to that of the C-terminal domain in the crystal structure of Mpro. Interestingly, the Mpro-C dimer structure is characterized by 3D domain-swapping, in which the first helices of the two protomers are interchanged and each is enwrapped by four other helices from the other protomer. Each folding subunit of the Mpro-C domain-swapped dimer still has the same general fold as that of the Mpro-C monomer. This special dimerization elucidates the structural basis for the observation that there is no exchange between monomeric and dimeric forms of Mpro-C and Mpro-D7.
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