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PDBsum entry 5mv0
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Viral protein
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PDB id
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5mv0
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References listed in PDB file
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Key reference
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Title
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Structural insights into reptarenavirus cap-Snatching machinery.
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Authors
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M.Rosenthal,
N.Gogrefe,
D.Vogel,
J.Reguera,
B.Rauschenberger,
S.Cusack,
S.Günther,
S.Reindl.
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Ref.
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PLoS Pathog, 2017,
13,
e1006400.
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PubMed id
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Abstract
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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
endonuclease in the N-terminus of CASV L protein. It shows a typical
endonuclease fold with an active site configuration that is essentially
identical to that of known mammarenavirus endonuclease structures. In
conclusion, we provide evidence for a presumably functional cap-snatching
endonuclease in the N-terminus and a degenerate cap-binding domain in the
C-terminus of a reptarenavirus L protein. Implications of these findings for the
cap-snatching mechanism in arenaviruses are discussed.
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