Your browser doesn't support javascript.
loading
CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.
Gupta, Meghna; Azumaya, Caleigh M; Moritz, Michelle; Pourmal, Sergei; Diallo, Amy; Merz, Gregory E; Jang, Gwendolyn; Bouhaddou, Mehdi; Fossati, Andrea; Brilot, Axel F; Diwanji, Devan; Hernandez, Evelyn; Herrera, Nadia; Kratochvil, Huong T; Lam, Victor L; Li, Fei; Li, Yang; Nguyen, Henry C; Nowotny, Carlos; Owens, Tristan W; Peters, Jessica K; Rizo, Alexandrea N; Schulze-Gahmen, Ursula; Smith, Amber M; Young, Iris D; Yu, Zanlin; Asarnow, Daniel; Billesbølle, Christian; Campbell, Melody G; Chen, Jen; Chen, Kuei-Ho; Chio, Un Seng; Dickinson, Miles Sasha; Doan, Loan; Jin, Mingliang; Kim, Kate; Li, Junrui; Li, Yen-Li; Linossi, Edmond; Liu, Yanxin; Lo, Megan; Lopez, Jocelyne; Lopez, Kyle E; Mancino, Adamo; Moss, Frank R; Paul, Michael D; Pawar, Komal Ishwar; Pelin, Adrian; Pospiech, Thomas H; Puchades, Cristina.
Afiliación
  • Gupta M; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Azumaya CM; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Moritz M; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Pourmal S; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Diallo A; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Merz GE; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Jang G; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Bouhaddou M; QBI, University of California, San Francisco, CA 94158, USA.
  • Fossati A; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Brilot AF; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Diwanji D; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Hernandez E; QBI, University of California, San Francisco, CA 94158, USA.
  • Herrera N; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Kratochvil HT; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Lam VL; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Li F; QBI, University of California, San Francisco, CA 94158, USA.
  • Li Y; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Nguyen HC; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Nowotny C; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Owens TW; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Peters JK; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Rizo AN; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Schulze-Gahmen U; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Smith AM; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Young ID; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Yu Z; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Asarnow D; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Billesbølle C; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Campbell MG; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Chen J; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Chen KH; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Chio US; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Dickinson MS; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Doan L; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Jin M; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Kim K; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Li J; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Li YL; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Linossi E; Current affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Liu Y; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Lo M; Quantitative Biosciences Institute (QBI) COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA.
  • Lopez J; QBI, University of California, San Francisco, CA 94158, USA.
  • Lopez KE; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
  • Mancino A; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Moss FR; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Paul MD; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Pawar KI; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Pelin A; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Pospiech TH; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
  • Puchades C; QBI Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA 94158, USA.
Res Sq ; 2021 May 19.
Article en En | MEDLINE | ID: mdl-34031651
The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos