Structural insights into reptarenavirus cap-snatching machinery

PLoS Pathogens
Maria RosenthalSophia Reindl

Abstract

Cap-snatching was first discovered in influenza virus. Structures of the involved domains of the influenza virus polymerase, namely the endonuclease in the PA subunit and the cap-binding domain in the PB2 subunit, have been solved. Cap-snatching endonucleases have also been demonstrated at the very N-terminus of the L proteins of mammarena-, orthobunya-, and hantaviruses. However, a cap-binding domain has not been identified in an arena- or bunyavirus L protein so far. We solved the structure of the 326 C-terminal residues of the L protein of California Academy of Sciences virus (CASV), a reptarenavirus, by X-ray crystallography. The individual domains of this 37-kDa fragment (L-Cterm) as well as the domain arrangement are structurally similar to the cap-binding and adjacent domains of influenza virus polymerase PB2 subunit, despite the absence of sequence homology, suggesting a common evolutionary origin. This enabled identification of a region in CASV L-Cterm with similarity to a cap-binding site; however, the typical sandwich of two aromatic residues was missing. Consistent with this, cap-binding to CASV L-Cterm could not be detected biochemically. In addition, we solved the crystal structure of the corresponding endonucleas...Continue Reading

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Citations

Mar 31, 2019·The Journal of Biological Chemistry·Dominik VogelStephan Günther
May 29, 2019·PLoS Pathogens·Nadja GogrefeMaria Rosenthal
Mar 28, 2020·Nature·Ruchao PengYi Shi
Jul 28, 2020·Viruses·Nicolas PapageorgiouFrançois Ferron
Mar 29, 2019·Frontiers in Immunology·Morgan E Brisse, Hinh Ly
Apr 30, 2019·Wiley Interdisciplinary Reviews. RNA·Shaun T CrossJeffrey Wilusz
Jun 3, 2021·Viruses·Richard KormelinkCecile Desbiez
Aug 29, 2021·Viruses·Kristina MeierMaria Rosenthal
Aug 26, 2021·Journal of Virology·Jesse D Pyle, Sean P J Whelan

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Methods Mentioned

BETA
size exclusion chromatography
size-exclusion chromatography
pull-down
thermal shift
affinity
in vitro transcription
electrophoresis
X-ray
transfection
Assay

Software Mentioned

ClustalOmega
PHENIX
DAMMIF
GNOM
Cellscript
PyMOL ( PyMOL Molecular Graphics System
SUPCOMB
MUSCLE
PyMOL
DAMAVER

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