6o3v
From Proteopedia
Crystal structure for RVA-VP3
Structural highlights
Function[Q1WK45_9REOV] Counteracts the host innate immune response thanks to its phosphodiesterase that degrades the 5'-triphosphorylated, 2'-5' linked adenylate oligomers produced by the host cell IFN-inducible 2',5'-oligoadenylate synthetase (OAS). The host RNaseL is therefore not activated.[HAMAP-Rule:MF_04128] Multifunctional enzyme involved in mRNA capping. Catalyzes the formation of the 5' cap structure on the viral plus-strand transcripts. Specifically binds to GTP and displays guanylyltransferase and methyltransferase activities. Has affinity for ssRNA but not for dsRNA. Capping activity is non-specific and caps RNAs that initiate with either a G or an A residue. Together with VP1 polymerase, forms a VP1-VP3 complex positioned near the channels situated at each of the five-fold vertices of the core. Following infection, the outermost layer of the virus is lost, leaving a double-layered particle (DLP) made up of the core and VP6 shell. VP1 then catalyzes the transcription of fully conservative plus-strand genomic RNAs that are capped by VP3 and extruded through the DLP's channels into the cytoplasm where they function as mRNAs for translation of viral proteins. DLPs probably have an RNA triphosphatase activity as well, whereas open cores do not.[HAMAP-Rule:MF_04128] Publication Abstract from PubMedIn many viruses, including rotavirus (RV), the major pathogen of infantile gastroenteritis, capping of viral messenger RNAs is a pivotal step for efficient translation of the viral genome. In RV, VP3 caps the nascent transcripts synthesized from the genomic dsRNA segments by the RV polymerase VP1 within the particle core. Here, from cryo-electron microscopy, x-ray crystallography, and biochemical analyses, we show that VP3 forms a stable tetrameric assembly with each subunit having a modular domain organization, which uniquely integrates five distinct enzymatic steps required for capping the transcripts. In addition to the previously known guanylyl- and methyltransferase activities, we show that VP3 exhibits hitherto unsuspected RNA triphosphatase activity necessary for initiating transcript capping and RNA helicase activity likely required for separating the RNA duplex formed transiently during endogenous transcription. From our studies, we propose a new mechanism for how VP3 inside the virion core caps the nascent transcripts exiting from the polymerase. 2.7 A cryo-EM structure of rotavirus core protein VP3, a unique capping machine with a helicase activity.,Kumar D, Yu X, Crawford SE, Moreno R, Jakana J, Sankaran B, Anish R, Kaundal S, Hu L, Estes MK, Wang Z, Prasad BVV Sci Adv. 2020 Apr 15;6(16):eaay6410. doi: 10.1126/sciadv.aay6410. eCollection, 2020 Apr. PMID:32494598[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Group a rotaviruses | Large Structures | Hu, L | Kumar, D | Prasad, V | Wang, Z | Yu, X | Capping enzyme | Guanylyl transferase | Methyl transferase | Pde | Rotavirus | Rtpase | Structural protein | Vp3
