Selenoprotein S Interacts with the Replication and Transcription Complex of SARS-CoV-2 by Binding nsp7.
Selenoprotein S Interacts with the Replication and Transcription Complex of SARS-CoV-2 by Binding nsp7.
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DOI：
10.1016/j.jmb.2023.168008
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发表时间：
2023-04-15
影响因子：
5.6
通讯作者：
Rozovsky, Sharon
中科院分区：
文献类型：
--
作者：
Ghelichkhani, Farid;Gonzalez, Fabio A.;Kapitonova, Mariia A.;Rozovsky, Sharon
严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 使用内质网膜及其相关蛋白质机制进行复制并逃避检测。这些被劫持的人类蛋白质包括硒蛋白 S (selenos)。这种硒蛋白参与蛋白质质量控制、信号传导和细胞因子分泌的调节。虽然硒在病毒生命周期中的作用尚不清楚，但据报道它与 SARS-CoV-2 非结构蛋白 7 (nsp7) 相互作用，后者是病毒复制所必需的病毒蛋白。我们开始研究 selenos 和 nsp7 是否直接相互作用，以及当 nsp7 与病毒的复制和转录复合物结合时它们是否仍然可以结合。通过生化分析，我们发现 Selenos 直接与 nsp7 结合。此外，我们发现，当 nsp7 与冠状病毒的最小复制和转录复合物形成复合物时，selenos 可以与 nsp7 结合，该复合物由 nsp7、nsp8 和 RNA 依赖性 RNA 聚合酶 nsp12 组成。此外，通过交联实验，我们绘制了复制复合物中selenos和nsp7的相互作用位点，并表明selenos的疏水片段对于与nsp7的结合至关重要。这种排列留下了延伸的螺旋和本质上无序的硒代片段（包括反应性硒代半胱氨酸），并自由地潜在地招募额外的蛋白质到复制和转录复合物中。
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates and evades detection using ER membranes and their associated protein machinery. Among these hijacked human proteins is selenoprotein S (selenos). This selenoprotein takes part in the protein quality control, signaling, and the regulation of cytokine secretion. While the role of selenos in the viral life cycle is not yet known, it has been reported to interact with SARS-CoV-2 nonstructural protein 7 (nsp7), a viral protein essential for the replication of the virus. We set to study whether selenos and nsp7 interact directly and if they can still bind when nsp7 is bound to the replication and transcription complex of the virus. Using biochemical assays, we show that selenos binds directly to nsp7. In addition, we found that selenos can bind to nsp7 when it is in a complex with the coronavirus's minimal replication and transcription complex, comprised of nsp7, nsp8, and the RNA-dependent RNA polymerase nsp12. In addition, through crosslinking experiments, we mapped the interaction sites of selenos and nsp7 in the replication complex and showed that the hydrophobic segment of selenos is essential for binding to nsp7. This arrangement leaves an extended helix and the intrinsically disordered segment of selenos—including the reactive selenocysteine—exposed and free to potentially recruit additional proteins to the replication and transcription complex.
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影响因子：
4.5
作者：
Gao Y;Xie X;Ma YT;Yang YN;Li XM;Fu ZY;Zheng YY;Ma X;Chen BD;Liu F;Huang Y
通讯作者：
Huang Y
影响因子：
64.8
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Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
7.7
作者：
Gao, Y;Walder, K;Collier, GR
通讯作者：
Collier, GR
DOI：
10.1126/science.abe9403
发表时间：
2020-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gordon DE;Hiatt J;Bouhaddou M;Rezelj VV;Ulferts S;Braberg H;Jureka AS;Obernier K;Guo JZ;Batra J;Kaake RM;Weckstein AR;Owens TW;Gupta M;Pourmal S;Titus EW;Cakir M;Soucheray M;McGregor M;Cakir Z;Jang G;O'Meara MJ;Tummino TA;Zhang Z;Foussard H;Rojc A;Zhou Y;Kuchenov D;Hüttenhain R;Xu J;Eckhardt M;Swaney DL;Fabius JM;Ummadi M;Tutuncuoglu B;Rathore U;Modak M;Haas P;Haas KM;Naing ZZC;Pulido EH;Shi Y;Barrio-Hernandez I;Memon D;Petsalaki E;Dunham A;Marrero MC;Burke D;Koh C;Vallet T;Silvas JA;Azumaya CM;Billesbølle C;Brilot AF;Campbell MG;Diallo A;Dickinson MS;Diwanji D;Herrera N;Hoppe N;Kratochvil HT;Liu Y;Merz GE;Moritz M;Nguyen HC;Nowotny C;Puchades C;Rizo AN;Schulze-Gahmen U;Smith AM;Sun M;Young ID;Zhao J;Asarnow D;Biel J;Bowen A;Braxton JR;Chen J;Chio CM;Chio US;Deshpande I;Doan L;Faust B;Flores S;Jin M;Kim K;Lam VL;Li F;Li J;Li YL;Li Y;Liu X;Lo M;Lopez KE;Melo AA;Moss FR 3rd;Nguyen P;Paulino J;Pawar KI;Peters JK;Pospiech TH Jr;Safari M;Sangwan S;Schaefer K;Thomas PV;Thwin AC;Trenker R;Tse E;Tsui TKM;Wang F;Whitis N;Yu Z;Zhang K;Zhang Y;Zhou F;Saltzberg D;QCRG Structural Biology Consortium;Hodder AJ;Shun-Shion AS;Williams DM;White KM;Rosales R;Kehrer T;Miorin L;Moreno E;Patel AH;Rihn S;Khalid MM;Vallejo-Gracia A;Fozouni P;Simoneau CR;Roth TL;Wu D;Karim MA;Ghoussaini M;Dunham I;Berardi F;Weigang S;Chazal M;Park J;Logue J;McGrath M;Weston S;Haupt R;Hastie CJ;Elliott M;Brown F;Burness KA;Reid E;Dorward M;Johnson C;Wilkinson SG;Geyer A;Giesel DM;Baillie C;Raggett S;Leech H;Toth R;Goodman N;Keough KC;Lind AL;Zoonomia Consortium;Klesh RJ;Hemphill KR;Carlson-Stevermer J;Oki J;Holden K;Maures T;Pollard KS;Sali A;Agard DA;Cheng Y;Fraser JS;Frost A;Jura N;Kortemme T;Manglik A;Southworth DR;Stroud RM;Alessi DR;Davies P;Frieman MB;Ideker T;Abate C;Jouvenet N;Kochs G;Shoichet B;Ott M;Palmarini M;Shokat KM;García-Sastre A;Rassen JA;Grosse R;Rosenberg OS;Verba KA;Basler CF;Vignuzzi M;Peden AA;Beltrao P;Krogan NJ
通讯作者：
Krogan NJ
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE