5EFC

Structure of Influenza B Lee PB2 cap-binding domain bound to GTP

5EFC の概要

• エントリーDOI: 10.2210/pdb5efc/pdb
• 関連するPDBエントリー: 5EF9 5EFA
• 分子名称: Polymerase basic protein 2, GUANOSINE-5'-TRIPHOSPHATE (3 entities in total)
• 機能のキーワード: cap-binding domain, protein binding
• 由来する生物種: Influenza B virus
• 細胞内の位置: Virion: Q9QLL6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20964.71

構造登録者

Ma, X.,Shia, S. (登録日: 2015-10-23, 公開日: 2015-11-18, 最終更新日: 2024-03-06)

主引用文献

Xie, L.,Wartchow, C.,Shia, S.,Uehara, K.,Steffek, M.,Warne, R.,Sutton, J.,Muiru, G.T.,Leonard, V.H.,Bussiere, D.E.,Ma, X.
Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit.
J.Biol.Chem., 291:363-370, 2016

PubMed Abstract: Influenza virus polymerase catalyzes the transcription of viral mRNAs by a process known as "cap-snatching," where the 5'-cap of cellular pre-mRNA is recognized by the PB2 subunit and cleaved 10-13 nucleotides downstream of the cap by the endonuclease PA subunit. Although this mechanism is common to both influenza A (FluA) and influenza B (FluB) viruses, FluB PB2 recognizes a wider range of cap structures including m(7)GpppGm-, m(7)GpppG-, and GpppG-RNA, whereas FluA PB2 utilizes methylated G-capped RNA specifically. Biophysical studies with isolated PB2 cap-binding domain (PB2(cap)) confirm that FluB PB2 has expanded mRNA cap recognition capability, although the affinities toward m(7)GTP are significantly reduced when compared with FluA PB2. The x-ray co-structures of the FluB PB2(cap) with bound cap analogs m(7)GTP and GTP reveal an inverted GTP binding mode that is distinct from the cognate m(7)GTP binding mode shared between FluA and FluB PB2. These results delineate the commonalities and differences in the cap-binding site between FluA and FluB PB2 and will aid structure-guided drug design efforts to identify dual inhibitors of both FluA and FluB PB2.

PubMed: 26559973
DOI: 10.1074/jbc.M115.693051

実験手法

X-RAY DIFFRACTION (1.9 Å)