%0 Journal Article
%T Structural insights into reptarenavirus cap-snatching machinery
%A Bianka Rauschenberger
%A Dominik Vogel
%A Juan Reguera
%A Maria Rosenthal
%A Nadja Gogrefe
%A Sophia Reindl
%A Stephan G¨šnther
%A Stephen Cusack
%J -
%D 2017
%R 10.1371/journal.ppat.1006400
%X 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
%K Crystal structure
%K Sequence alignment
%K Influenza viruses
%K Viral structure
%K Protein structure comparison
%K Protein structure
%K Arenaviruses
%K Protein structure determination
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006400