2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
Abstract
The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5'-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2'-O position of the first nucleotide. To investigate the conformational changes of the complex during 2'-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog (m7GpppAm2'-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.
- Authors:
-
[2];
[3];
[4];
[3];
[2];
[4];
[3];
[2];
[4];
[3];
- Univ. of Chicago, IL (United States); Jagiellonian Univ., Krakow (Poland)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Northwestern Univ., Evanston, IL (United States)
- Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH); U.S. Department of Treasury
- OSTI Identifier:
- 1787334
- Grant/Contract Number:
- AC02-06CH11357; HHSN272201700060C
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 118; Journal Issue: 21; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; CAP-1; Nsp10/16; SARS-CoV-2; mRNA; serial crystallography
Citation Formats
Wilamowski, Mateusz, Sherrell, Darren A., Minasov, George, Kim, Youngchang, Shuvalova, Ludmilla, Lavens, Alex, Chard, Ryan, Maltseva, Natalia, Jedrzejczak, Robert, Rosas-Lemus, Monica, Saint, Nickolaus, Foster, Ian T., Michalska, Karolina, Satchell, Karla F., and Joachimiak, Andrzej. 2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography. United States: N. p., 2021.
Web. doi:10.1073/pnas.2100170118.
Wilamowski, Mateusz, Sherrell, Darren A., Minasov, George, Kim, Youngchang, Shuvalova, Ludmilla, Lavens, Alex, Chard, Ryan, Maltseva, Natalia, Jedrzejczak, Robert, Rosas-Lemus, Monica, Saint, Nickolaus, Foster, Ian T., Michalska, Karolina, Satchell, Karla F., & Joachimiak, Andrzej. 2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography. United States. https://doi.org/10.1073/pnas.2100170118
Wilamowski, Mateusz, Sherrell, Darren A., Minasov, George, Kim, Youngchang, Shuvalova, Ludmilla, Lavens, Alex, Chard, Ryan, Maltseva, Natalia, Jedrzejczak, Robert, Rosas-Lemus, Monica, Saint, Nickolaus, Foster, Ian T., Michalska, Karolina, Satchell, Karla F., and Joachimiak, Andrzej. Mon .
"2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography". United States. https://doi.org/10.1073/pnas.2100170118. https://www.osti.gov/servlets/purl/1787334.
@article{osti_1787334,
title = {2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography},
author = {Wilamowski, Mateusz and Sherrell, Darren A. and Minasov, George and Kim, Youngchang and Shuvalova, Ludmilla and Lavens, Alex and Chard, Ryan and Maltseva, Natalia and Jedrzejczak, Robert and Rosas-Lemus, Monica and Saint, Nickolaus and Foster, Ian T. and Michalska, Karolina and Satchell, Karla F. and Joachimiak, Andrzej},
abstractNote = {The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5'-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2'-O position of the first nucleotide. To investigate the conformational changes of the complex during 2'-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog (m7GpppAm2'-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.},
doi = {10.1073/pnas.2100170118},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 21,
volume = 118,
place = {United States},
year = {Mon May 10 00:00:00 EDT 2021},
month = {Mon May 10 00:00:00 EDT 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Crystal structure of SARS-CoV-2 nsp10/nsp16 2′-O-methylase and its implication on antiviral drug design
journal, July 2020
- Lin, Sheng; Chen, Hua; Ye, Fei
- Signal Transduction and Targeted Therapy, Vol. 5, Issue 1
MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes
journal, July 2004
- Davis, I. W.; Murray, L. W.; Richardson, J. S.
- Nucleic Acids Research, Vol. 32, Issue Web Server
Crystal Structure of Guanidinoacetate Methyltransferase from Rat Liver: A Model Structure of Protein Arginine Methyltransferase
journal, July 2002
- Komoto, Junichi; Huang, Yafei; Takata, Yoshimi
- Journal of Molecular Biology, Vol. 320, Issue 2
Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex
journal, May 2011
- Decroly, Etienne; Debarnot, Claire; Ferron, François
- PLoS Pathogens, Vol. 7, Issue 5
Efficient and Secure Transfer, Synchronization, and Sharing of Big Data
journal, September 2014
- Chard, Kyle; Tuecke, Steven; Foster, Ian
- IEEE Cloud Computing, Vol. 1, Issue 3
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
journal, February 2020
- Huang, Chaolin; Wang, Yeming; Li, Xingwang
- The Lancet, Vol. 395, Issue 10223
A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA
journal, July 2015
- Schuberth-Wagner, Christine; Ludwig, Janos; Bruder, Ann Kristin
- Immunity, Vol. 43, Issue 1
Petrel: A Programmatically Accessible Research Data Service
conference, July 2019
- Allcock, William E.; Allen, Benjamin S.; Ananthakrishnan, Rachana
- PEARC '19: Practice and Experience in Advanced Research Computing, Proceedings of the Practice and Experience in Advanced Research Computing on Rise of the Machines (learning)
RNA methyltransferases involved in 5′ cap biosynthesis
journal, December 2014
- Byszewska, Magdalena; Śmietański, Mirosław; Purta, Elżbieta
- RNA Biology, Vol. 11, Issue 12
Globus platform-as-a-service for collaborative science applications: GLOBUS PLATFORM-AS-A-SERVICE FOR COLLABORATIVE SCIENCE APPLICATIONS
journal, March 2014
- Ananthakrishnan, Rachana; Chard, Kyle; Foster, Ian
- Concurrency and Computation: Practice and Experience, Vol. 27, Issue 2
Nylon mesh-based sample holder for fixed-target serial femtosecond crystallography
journal, May 2019
- Lee, Donghyeon; Baek, Sangwon; Park, Jaehyun
- Scientific Reports, Vol. 9, Issue 1
Structural basis of RNA cap modification by SARS-CoV-2
journal, July 2020
- Viswanathan, Thiruselvam; Arya, Shailee; Chan, Siu-Hong
- Nature Communications, Vol. 11, Issue 1
Mediation of donor–acceptor distance in an enzymatic methyl transfer reaction
journal, June 2015
- Zhang, Jianyu; Kulik, Heather J.; Martinez, Todd J.
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 26
In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation
journal, April 2010
- Bouvet, Mickaël; Debarnot, Claire; Imbert, Isabelle
- PLoS Pathogens, Vol. 6, Issue 4
SARS — beginning to understand a new virus
journal, December 2003
- Stadler, Konrad; Masignani, Vega; Eickmann, Markus
- Nature Reviews Microbiology, Vol. 1, Issue 3
funcX: A Federated Function Serving Fabric for Science
conference, June 2020
- Chard, Ryan; Babuji, Yadu; Li, Zhuozhao
- HPDC '20: The 29th International Symposium on High-Performance Parallel and Distributed Computing, Proceedings of the 29th International Symposium on High-Performance Parallel and Distributed Computing
Coronavirus non-structural protein 16: Evasion, attenuation, and possible treatments
journal, December 2014
- Menachery, Vineet D.; Debbink, Kari; Baric, Ralph S.
- Virus Research, Vol. 194
Parsl: Pervasive Parallel Programming in Python
conference, January 2019
- Babuji, Yadu; Foster, Ian; Wilde, Michael
- Proceedings of the 28th International Symposium on High-Performance Parallel and Distributed Computing - HPDC '19
Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex
journal, October 2011
- Chen, Yu; Su, Ceyang; Ke, Min
- PLoS Pathogens, Vol. 7, Issue 10
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I
journal, January 2016
- Devarkar, Swapnil C.; Wang, Chen; Miller, Matthew T.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 3
2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members
journal, November 2010
- Daffis, Stephane; Szretter, Kristy J.; Schriewer, Jill
- Nature, Vol. 468, Issue 7322
Low-dose fixed-target serial synchrotron crystallography
journal, March 2017
- Owen, Robin L.; Axford, Danny; Sherrell, Darren A.
- Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 4, p. 373-378
Binding of the Methyl Donor S-Adenosyl-l-Methionine to Middle East Respiratory Syndrome Coronavirus 2′-O-Methyltransferase nsp16 Promotes Recruitment of the Allosteric Activator nsp10
journal, December 2016
- Aouadi, Wahiba; Blanjoie, Alexandre; Vasseur, Jean-Jacques
- Journal of Virology, Vol. 91, Issue 5
The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure
journal, July 2018
- Martin, Baptiste; Coutard, Bruno; Guez, Théo
- Nucleic Acids Research, Vol. 46, Issue 15
Influence of 5'-terminal cap structure on the initiation of translation of vaccinia virus mRNA.
journal, March 1978
- Muthukrishnan, S.; Moss, B.; Cooper, J. A.
- Journal of Biological Chemistry, Vol. 253, Issue 5
REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011
- Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
CheckMyMetal : a macromolecular metal-binding validation tool
journal, February 2017
- Zheng, Heping; Cooper, David R.; Porebski, Przemyslaw J.
- Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 3
Coronavirus Nonstructural Protein 16 Is a Cap-0 Binding Enzyme Possessing (Nucleoside-2′O)-Methyltransferase Activity
journal, April 2008
- Decroly, Etienne; Imbert, Isabelle; Coutard, Bruno
- Journal of Virology, Vol. 82, Issue 16
Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
journal, January 2011
- Züst, Roland; Cervantes-Barragan, Luisa; Habjan, Matthias
- Nature Immunology, Vol. 12, Issue 2
An interactive web-based dashboard to track COVID-19 in real time
journal, May 2020
- Dong, Ensheng; Du, Hongru; Gardner, Lauren
- The Lancet Infectious Diseases, Vol. 20, Issue 5
Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin
journal, July 2020
- Krafcikova, Petra; Silhan, Jan; Nencka, Radim
- Nature Communications, Vol. 11, Issue 1
S -Adenosyl-Methionine-Dependent Methyltransferases: Highly Versatile Enzymes in Biocatalysis, Biosynthesis and Other Biotechnological Applications
journal, November 2012
- Struck, Anna-Winona; Thompson, Mark L.; Wong, Lu Shin
- ChemBioChem, Vol. 13, Issue 18
Room Temperature Structure of SARS-CoV-2 Nsp10/Nsp16 Methyltransferase in a Complex with m7GpppA Cap-0 and SAM Determined by Fixed-Target Serial Crystallography
text, January 2020
- Wilamowski, M.; Sherrell, D. A.; Minasov, G.
- Worldwide Protein Data Bank
In silico identification, structure prediction and phylogenetic analysis of the 2′-O-ribose (cap 1) methyltransferase domain in the large structural protein of ssRNA negative-strand viruses
journal, February 2002
- Bujnicki, Janusz M.; Rychlewski, Leszek
- Protein Engineering, Design and Selection, Vol. 15, Issue 2
High-resolution structures of the SARS-CoV-2 2′- O -methyltransferase reveal strategies for structure-based inhibitor design
journal, September 2020
- Rosas-Lemus, Monica; Minasov, George; Shuvalova, Ludmilla
- Science Signaling, Vol. 13, Issue 651
Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China
journal, March 2020
- Wu, Aiping; Peng, Yousong; Huang, Baoying
- Cell Host & Microbe, Vol. 27, Issue 3
The Role of the Cap Structure in RNA Processing and Nuclear Export
journal, July 1997
- Lewis, Joe D.; Izaurflde, Elisa
- European Journal of Biochemistry, Vol. 247, Issue 2
Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals
journal, March 2015
- Uervirojnangkoorn, Monarin; Zeldin, Oliver B.; Lyubimov, Artem Y.
- eLife, Vol. 4
Molecular phylogenetics of the RrmJ/fibrillarin superfamily of ribose 2′-O-methyltransferases
journal, January 2003
- Feder, Marcin; Pas, Jakub; Wyrwicz, Lucjan S.
- Gene, Vol. 302, Issue 1-2