4uaf

From Proteopedia

Importin alpha 1 delta IBB in complex with Influenza PB2 nuclear localization domain

PDB ID 4uaf

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Structural highlights

4uaf is a 2 chain structure with sequence from Influenza A virus (A/Victoria/3/1975(H3N2)) and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.698Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PB2_I75A3 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 PubMed

Influenza A virus polymerase subunit PB2 is a major virulence determinant implicated in pathogenicity and host adaptation. During cross-species virus transfer from avian to mammalian cells, PB2 switches specificity from importin alpha3 to alpha7. This specificity is not recapitulated in vitro, where PB2 binds all importin alpha isoforms with comparably high affinity. In this study, we investigated the structure, conformational dynamics, and autoinhibition of importin alpha isoforms 1, 3, and 7 in complex with PB2. Our data suggest that association of PB2 with alpha3 and alpha7 is favored by reduced autoinhibition of these isoforms and by the unique structure of the nuclear localization signal (NLS) domain of PB2. We propose that by recruiting importin alpha3 or alpha7 in the absence of importin beta, PB2 reduces the complexity of adaptor-mediated import to a pseudo-bimolecular reaction, thereby acquiring a kinetic advantage over classical NLS cargos, which form an import complex only when importin alpha and beta are simultaneously available.

Molecular Determinants for Nuclear Import of Influenza A PB2 by Importin alpha Isoforms 3 and 7.,Pumroy RA, Ke S, Hart DJ, Zachariae U, Cingolani G Structure. 2015 Feb 3;23(2):374-84. doi: 10.1016/j.str.2014.11.015. Epub 2015 Jan, 15. PMID:25599645^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pumroy RA, Ke S, Hart DJ, Zachariae U, Cingolani G. Molecular Determinants for Nuclear Import of Influenza A PB2 by Importin alpha Isoforms 3 and 7. Structure. 2015 Feb 3;23(2):374-84. doi: 10.1016/j.str.2014.11.015. Epub 2015 Jan, 15. PMID:25599645 doi:http://dx.doi.org/10.1016/j.str.2014.11.015