Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase

Lee, Eunhye; Bujalowski, Paul J.; Teramoto, Tadahisa; Gottipati, Keerthi; Scott, Seth D.; Padmanabhan, Radhakrishnan; Choi, Kyung H.

doi:10.1038/s41467-021-22846-1

Title: Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase

Journal Article · Wed May 05 00:00:00 EDT 2021 · Nature Communications

DOI:https://doi.org/10.1038/s41467-021-22846-1· OSTI ID:1783907

Lee, Eunhye ^[1]; Bujalowski, Paul J. ^[1]; Teramoto, Tadahisa ^[2]; Gottipati, Keerthi ^[1];

^[1];

^[2];

^[1]

University of Texas Medical Branch, Galveston, TX (United States)
Georgetown Univ., Washington, DC (United States). School of Medicine

Flaviviruses use a ~70 nucleotide stem-loop structure called stem-loop A (SLA) at the 5' end of the RNA genome as a promoter for RNA synthesis. Flaviviral polymerase NS5 specifically recognizes SLA to initiate RNA synthesis and methylate the 5' guanosine cap. We report the crystal structures of dengue (DENV) and Zika virus (ZIKV) SLAs. DENV and ZIKV SLAs differ in the relative orientations of their top stem-loop helices to bottom stems, but both form an intermolecular three-way junction with a neighboring SLA molecule. To understand how NS5 engages SLA, we determined the SLA-binding site on NS5 and modeled the NS5-SLA complex of DENV and ZIKV. Our results show that the gross conformational differences seen in DENV and ZIKV SLAs can be compensated by the differences in the domain arrangements in DENV and ZIKV NS5s. We describe two binding modes of SLA and NS5 and propose an SLA-mediated RNA synthesis mechanism.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Michigan Economic Development Corporation; Michigan Technology Tri-Corridor

Grant/Contract Number:: AC02-06CH11357; R01 AI087856; R21 AI137627; 085P1000817

OSTI ID:: 1783907

Journal Information:: Nature Communications, Vol. 12, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Title: Structures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase

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