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C‐terminal domain of SARS‐CoV main protease can form a 3D domain‐swapped dimer
Author(s) -
Zhong Nan,
Zhang Shengnan,
Xue Fei,
Kang Xue,
Zou Peng,
Chen Jiaxuan,
Liang Chao,
Rao Zihe,
Jin Changwen,
Lou Zhiyong,
Xia Bin
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.76
Subject(s) - polyproteins , dimer , monomer , chemistry , protein subunit , folding (dsp implementation) , domain (mathematical analysis) , c terminus , crystallography , stereochemistry , protein folding , protein structure , protease , viral protein , biophysics , biology , biochemistry , enzyme , virology , virus , amino acid , mathematical analysis , mathematics , organic chemistry , gene , electrical engineering , engineering , polymer
SARS coronavirus main protease (M pro ) 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 M pro C‐terminal domain alone (M pro ‐C) and the N‐finger deletion mutant of M pro (M pro ‐Δ7) exist as a stable dimer and a stable monomer (Zhong et al., J Virol 2008; 82:4227‐4234). Here, we report structures of both M pro ‐C monomer and dimer. The structure of the M pro ‐C monomer is almost identical to that of the C‐terminal domain in the crystal structure of M pro . Interestingly, the M pro ‐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 M pro ‐C domain‐swapped dimer still has the same general fold as that of the M pro ‐C monomer. This special dimerization elucidates the structural basis for the observation that there is no exchange between monomeric and dimeric forms of M pro ‐C and M pro ‐Δ7.