4UAE

Importin alpha 3 delta IBB in complex with Influenza PB2 Nuclear Localization Domain

Summary for 4UAE

• Entry DOI: 10.2210/pdb4uae/pdb
• Related: 4UAD
• Descriptor: Importin subunit alpha-3, Polymerase basic protein 2, SULFATE ION, ... (4 entities in total)
• Functional Keywords: importin karyopherin complex nls, protein transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 55729.44

Authors

Pumroy, R.A.,Cingolani, G. (deposition date: 2014-08-08, release date: 2015-02-04, Last modification date: 2023-12-27)

Primary citation

Pumroy, R.A.,Ke, S.,Hart, D.J.,Zachariae, U.,Cingolani, G.
Molecular Determinants for Nuclear Import of Influenza A PB2 by Importin alpha Isoforms 3 and 7.
Structure, 23:374-384, 2015

PubMed Abstract: 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 α3 to α7. This specificity is not recapitulated in vitro, where PB2 binds all importin α isoforms with comparably high affinity. In this study, we investigated the structure, conformational dynamics, and autoinhibition of importin α isoforms 1, 3, and 7 in complex with PB2. Our data suggest that association of PB2 with α3 and α7 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 α3 or α7 in the absence of importin β, 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 α and β are simultaneously available.

PubMed: 25599645
DOI: 10.1016/j.str.2014.11.015

Experimental method

X-RAY DIFFRACTION (2.7 Å)