Structure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E bindingStructure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E binding

dc.contributor.authorOjha, Manju
dc.contributor.authorVogt, Jeff
dc.contributor.authorDas, Naba Krishna
dc.contributor.authorRedmond, Emily
dc.contributor.authorSingh, Karndeep
dc.contributor.authorBanna, Hasan Al
dc.contributor.authorSadat, Tasnia
dc.contributor.authorKoirala, Deepak
dc.date.accessioned2024-02-06T16:08:42Z
dc.date.available2024-02-06T16:08:42Z
dc.date.issued2023-12-18
dc.description.abstractThe genomes of several plant viruses contain RNA structures at their 3′ ends called cap-independent translation enhancers (CITEs) that bind the host protein factors such as mRNA 5′ cap-binding protein eIF4E for promoting cap-independent genome translation. However, the structural basis of such 5′ cap-binding protein recognition by the uncapped RNA remains largely unknown. Here, we have determined the crystal structure of a 3′ CITE, panicum mosaic virus-like translation enhancer (PTE) from the saguaro cactus virus (SCV), using a Fab crystallization chaperone. The PTE RNA folds into a three-way junction architecture with a pseudoknot between the purine-rich R domain and pyrimidine-rich Y domain, which organizes the overall structure to protrude out a specific guanine nucleotide, G18, from the R domain that comprises a major interaction site for the eIF4E binding. The superimposable crystal structures of the wild-type, G18A, G18C, and G18U mutants suggest that the PTE scaffold is preorganized with the flipped-out G18 ready to dock into the eIF4E 5′ cap-binding pocket. The binding studies with wheat and human eIF4Es using gel electrophoresis and isothermal titration calorimetry, and molecular docking computation for the PTE–eIF4E complex demonstrated that the PTE structure essentially mimics the mRNA 5′ cap for eIF4E binding. Such 5′ cap mimicry by the uncapped and structured viral RNA highlights how viruses can exploit RNA structures to mimic the host protein-binding partners and bypass the canonical mechanisms for their genome translation, providing opportunities for a better understanding of virus-host interactions and non-canonical translation mechanisms found in many pathogenic RNA viruses.
dc.description.sponsorshipThis work was supported by the NIH (MIRA 1R35GM150869-01) and University of Maryland Baltimore County (start-up funds, START grant, and SURFF fellowship) to D.K. and partly by the NIH T32 grant (GM066706) to M.O., H.A.B., and N.K.D. The crystallographic work is based on research conducted at the NE-CAT beamlines, 24-ID-C, and 24-ID-E, funded by the National Institute of General Medical Sciences from the NIH (P30 GM124165). The Eiger 16 M detector on 24-ID-E is funded by an NIH-ORIP HEI grant (S10OD021527). This research used the Advanced Photon Source resources—a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. We thank Prof. Michael F. Summers, the University of Maryland Baltimore County, for kindly providing the ITC facility and critical feedback on the manuscript.
dc.description.urihttps://www.pnas.org/doi/full/10.1073/pnas.2313677121
dc.format.extent12 pages
dc.genrejournal articles
dc.identifier.citationOjha, Manju, Jeff Vogt, Naba Krishna Das, Emily Redmond, Karndeep Singh, Hasan Al Banna, Tasnia Sadat, and Deepak Koirala. “Structure of Saguaro Cactus Virus 3′ Translational Enhancer Mimics 5′ Cap for eIF4E Binding.” Proceedings of the National Academy of Sciences 121, no. 4 (January 23, 2024): e2313677121. https://doi.org/10.1073/pnas.2313677121.
dc.identifier.urihttps://doi.org/10.1073/pnas.2313677121
dc.identifier.urihttp://hdl.handle.net/11603/31562
dc.language.isoen_US
dc.publisherPNAS
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemistry & Biochemistry Department Collection
dc.relation.ispartofUMBC Student Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsCC BY-NC-ND 4.0 DEED Attribution-NonCommercial-NoDerivs 4.0 International en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleStructure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E bindingStructure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E binding
dc.typeText
dcterms.creatorhttps://orcid.org/0009-0001-3907-431X
dcterms.creatorhttps://orcid.org/0009-0004-3001-9631
dcterms.creatorhttps://orcid.org/0000-0002-5308-2746
dcterms.creatorhttps://orcid.org/0000-0001-7148-5816
dcterms.creatorhttps://orcid.org/0000-0001-7475-6706
dcterms.creatorhttps://orcid.org/0000-0001-6424-3173

Files

Original bundle

Now showing 1 - 2 of 2
Loading...
Thumbnail Image
Name:
ojha-et-al-2024-structure-of-saguaro-cactus-virus-3-translational-enhancer-mimics-5-cap-for-eif4e-binding.pdf
Size:
4.49 MB
Format:
Adobe Portable Document Format
Loading...
Thumbnail Image
Name:
pnas.2313677121.sapp.pdf
Size:
4.65 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.56 KB
Format:
Item-specific license agreed upon to submission
Description: