7v1d

Crystal structure of Omsk hemorrhagic fever virus NS5 MTase (in complex with SAH and GpppA)

spinqualitylabelsall models 7v1d, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v1d is a 1 chain structure with sequence from Omsk hemorrhagic fever virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.87Å Ligands: G3A, GOL, IPA, PEG, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C4TPE0_OHFV Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3.[PROSITE-ProRule:PRU00859] Publication Abstract from PubMed The positive-sense flavivirus RNA genome bears a cap 1 structure essential for RNA stability and viral protein translation, and the formation of cap 1 requires the virally encoded nonstructural protein NS5 harboring guanylyltransferase (GTase), cap guanine N7 methyltransferase (N7 MTase), and 5'-nucleotide ribose 2'-O MTase activities in its single-domain MTase module. Despite numerous MTase-containing structures reported, the structural evidence for a critical GMP-enzyme intermediate formation and RNA repositioning when transitioning among different reactions is missing. Here, we report 10 high-resolution MTase crystal structures of Omsk hemorrhagic fever virus (OHFV), a representative high-consequence tick-borne flavivirus, capturing previously unidentified GMP-arginine adduct structures and a rarely observed capped RNA conformation. These structures help us thread capping events in the canonical model with a structure-based hypothesis involving the flipping of the 5' nucleotide, while the observation of an m(7)GMP-arginine adduct is compatible with an alternate capping model that decouples the N7 and 2'-O methylation steps. IMPORTANCE The methyltransferase (MTase) domain of flavivirus NS5 is unique in harboring guanylyltransferase (GTase), N7 MTase, and 2'-O MTase activities, playing a central role in viral RNA capping. However, the detailed mechanisms of the multistep capping process remain elusive. Here, we report 10 crystal structures of a flavivirus MTase to help understand the guanylyl transfer from GTP to the GTase itself and the transition between guanylyl transfer and methylation steps. In particular, a previously unobserved GMP-arginine covalent intermediate was captured multiple times in MTase crystal soaking trials with GTP present in the soaking solution, supporting its role in bridging the guanylyl transfer from GTP to the GTase and subsequent transfer to the 5'-diphosphate RNA. Crystal Structures of Flavivirus NS5 Guanylyltransferase Reveal a GMP-Arginine Adduct.,Jia H, Zhong Y, Peng C, Gong P J Virol. 2022 Jun 27:e0041822. doi: 10.1128/jvi.00418-22. PMID:35758665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA