PDBsum entry 5efc

Protein binding

PDB id: 5efc

Contents

Protein chain

163 a.a.

Ligands

GTP

Waters ×98

PDB id:

5efc

Name:

Protein binding

Title:

Structure of influenza b lee pb2 cap-binding domain bound to gtp

Structure:

Polymerase basic protein 2. Chain: a. Fragment: cap-binding domain. Synonym: RNA-directed RNA polymerase subunit p3. Engineered: yes

Source:

Influenza b virus. Organism_taxid: 518987. Strain: b/lee/1940. Gene: pb2. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.90Å R-factor: 0.185 R-free: 0.227

Authors:

X.Ma,S.Shia

Key ref:

L.Xie et al. (2016). Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit. J Biol Chem, 291, 363-370. PubMed id: 26559973 DOI: 10.1074/jbc.M115.693051

Date:

23-Oct-15 Release date: 18-Nov-15

Protein chain

Q9QLL6  (PB2_INBLE) -  Polymerase basic protein 2 from Influenza B virus (strain B/Lee/1940)

Seq: 770 a.a.

Struc: 163 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M115.693051

J Biol Chem 291:363-370 (2016)

PubMed id: 26559973

Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit.

L.Xie, C.Wartchow, S.Shia, K.Uehara, M.Steffek, R.Warne, J.Sutton, G.T.Muiru, V.H.Leonard, D.E.Bussiere, X.Ma.

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.