5efa | pdb_00005efa
Structure of Influenza B Lee PB2 cap-binding domain bound to m7GTP
Structural highlights
Function[PB2_INBLE] Involved in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved by PB1. May play a role in genome replication (By similarity). Publication Abstract from PubMedInfluenza 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 B (FluB) viruses, FluB PB2 recognizes a wider range of cap structures including m7GpppGm-, m7GpppG-, and GpppG-RNA, while FluA PB2 utilizes methylated G-capped RNA specifically. Biophysical studies with isolated PB2 cap-binding domain (PB2cap) confirm that FluB PB2 has expanded mRNA cap recognition capability although the affinities towards m7GTP are significantly reduced when compared to FluA PB2. The X-ray co-structures of the FluB PB2cap with bound cap analogs m7GTP and GTP reveal an inverted GTP binding mode that is distinct from the cognate m7GTP 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. Molecular basis of mRNA cap recognition by Influenza B polymerase PB2 subunit.,Xie L, Wartchow C, Shia S, Uehara K, Steffek M, Warne R, Sutton J, Muiru GT, Leonard VH, Bussiere DE, Ma X J Biol Chem. 2015 Nov 11. pii: jbc.M115.693051. PMID:26559973[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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