Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism.
Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism.
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DOI：
10.1038/s41598-017-11736-6
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发表时间：
2017-09-12
影响因子：
4.6
通讯作者：
Choi S
中科院分区：
文献类型：
--
作者：
Batool M;Shah M;Patra MC;Yesudhas D;Choi S
Middle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host’s immune system. The immune evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses has been recently attributed to the involvement of MERS-CoV protein 4a (p4a) that masks the viral dsRNA. However, the structural mechanism of how p4a recognizes and establishes contacts with dsRNA is not well explained. In this study, we report a dynamic mechanism deployed by p4a to engage the viral dsRNA and make it unavailable to the host immune system. Multiple variants of p4a-dsRNA were created and investigated through extensive molecular dynamics procedures to highlight crucial interfacial residues that may be used as potential pharmacophores for future drug development. The structural analysis revealed that p4a exhibits a typical αβββα fold structure, as found in other dsRNA-binding proteins. The α1 helix and the β1-β2 loop play a crucial role in recognizing and establishing contacts with the minor grooves of dsRNA. Further, mutational and binding free energy analyses suggested that in addition to K63 and K67, two other residues, K27 and W45, might also be crucial for p4a-dsRNA stability.
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影响因子：
14.9
作者：
Chillemi, Giovanni;D'Annessa, Ilda;Fiorani, Paola;Losasso, Carmen;Benedetti, Piero;Desideri, Alessandro
通讯作者：
Desideri, Alessandro
影响因子：
12.8
作者：
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通讯作者：
Choi S
影响因子：
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作者：
Excler JL;Delvecchio CJ;Wiley RE;Williams M;Yoon IK;Modjarrad K;Boujelal M;Moorthy VS;Hersi AS;Kim JH;MERS-CoV Vaccine Working Group
通讯作者：
MERS-CoV Vaccine Working Group
影响因子：
2.7
作者：
Abuhammad, Areej;Al-Aqtash, Rua'a A.;Taha, Mutasem O.
通讯作者：
Taha, Mutasem O.
DOI：
10.1073/pnas.0402525101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Hoang, TX;Trovato, A;Maritan, A
通讯作者：
Maritan, A