5MUS

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

5MUS の概要

• エントリーDOI: 10.2210/pdb5mus/pdb
• 分子名称: L protein, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: arenavirus, polymerase, putative cap-binding, viral protein
• 由来する生物種: CAS virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75373.91

構造登録者

Rosenthal, M.,Gogrefe, N.,Reguera, J.,Vogel, D.,Rauschenberger, B.,Cusack, S.,Gunther, S.,Reindl, S. (登録日: 2017-01-14, 公開日: 2017-05-17, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.009 Å)