6QHG

Structure of the cap-binding domain of Rift Valley Fever virus L protein

6QHG の概要

• エントリーDOI: 10.2210/pdb6qhg/pdb
• 分子名称: Polymerase, 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: bunyavirus, viral polymerase, cap-binding, viral transcription, viral protein
• 由来する生物種: Rift valley fever virus (RVFV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28675.27

構造登録者

Gogrefe, N.,Reindl, S.,Gunther, S.,Rosenthal, M. (登録日: 2019-01-16, 公開日: 2019-05-22, 最終更新日: 2024-11-13)

主引用文献

Gogrefe, N.,Reindl, S.,Gunther, S.,Rosenthal, M.
Structure of a functional cap-binding domain in Rift Valley fever virus L protein.
Plos Pathog., 15:e1007829-e1007829, 2019

PubMed Abstract: Rift Valley fever virus (RVFV) belongs to the family of Phenuiviridae within the order of Bunyavirales. The virus may cause fatal disease both in livestock and humans, and therefore, is of great economical and public health relevance. In analogy to the influenza virus polymerase complex, the bunyavirus L protein is assumed to bind to and cleave off cap structures of cellular mRNAs to prime viral transcription. However, even though the presence of an endonuclease in the N-terminal domain of the L protein has been demonstrated for several bunyaviruses, there is no evidence for a cap-binding site within the L protein. We solved the structure of a C-terminal 117 amino acid-long domain of the RVFV L protein by X-ray crystallography. The overall fold of the domain shows high similarity to influenza virus PB2 cap-binding domain and the putative non-functional cap-binding domain of reptarenaviruses. Upon co-crystallization with m7GTP, we detected the cap-analogue bound between two aromatic side chains as it has been described for other cap-binding proteins. We observed weak but specific interaction with m7GTP rather than GTP in vitro using isothermal titration calorimetry. The importance of m7GTP-binding residues for viral transcription was validated using a RVFV minigenome system. In summary, we provide structural and functional evidence for a cap-binding site located within the L protein of a virus from the Bunyavirales order.

PubMed: 31136637
DOI: 10.1371/journal.ppat.1007829

実験手法

X-RAY DIFFRACTION (1.483 Å)