5MUZ

Structure of a C-terminal domain of a reptarenavirus L protein

Summary for 5MUZ

• Entry DOI: 10.2210/pdb5muz/pdb
• Related: 5MUS
• Descriptor: L protein (2 entities in total)
• Functional Keywords: arenavirus, polymerase, putative cap-binding, viral protein
• Biological source: CAS virus
• Total number of polymer chains: 2
• Total formula weight: 23456.22

Authors

Rosenthal, M.,Gogrefe, N.,Reguera, J.,Vogel, D.,Rauschenberger, B.,Cusack, S.,Gunther, S.,Reindl, S. (deposition date: 2017-01-14, release date: 2017-05-17, Last modification date: 2024-01-17)

Primary citation

Rosenthal, M.,Gogrefe, N.,Vogel, D.,Reguera, J.,Rauschenberger, B.,Cusack, S.,Gunther, S.,Reindl, S.
Structural insights into reptarenavirus cap-snatching machinery.
PLoS Pathog., 13:e1006400-e1006400, 2017

PubMed 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 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.

PubMed: 28505175
DOI: 10.1371/journal.ppat.1006400

Experimental method

X-RAY DIFFRACTION (1.776 Å)