PDBsum entry 4uaf

Protein binding

PDB id: 4uaf

Contents

Protein chains

425 a.a.

72 a.a.

Ligands

PO4 ×2

Waters ×470

PDB id:

4uaf

Name:

Protein binding

Title:

Importin alpha 1 delta ibb in complex with influenza pb2 nuclear localization domain

Structure:

Importin subunit alpha-1. Chain: b. Synonym: importin alpha p1,karyopherin subunit alpha-2,pendulin,pore targeting complex 58 kda subunit,ptac58,rag cohort protein 1,srp1- alpha. Engineered: yes. Polymerase basic protein 2. Chain: e. Synonym: RNA-directed RNA polymerase subunit p3.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: kpna2, rch1. Expressed in: escherichia coli. Expression_system_taxid: 562. Influenza a virus. Organism_taxid: 392809. Strain: a/victoria/3/1975 h3n2.

Resolution:

1.70Å R-factor: 0.165 R-free: 0.193

Authors:

R.A.Pumroy,G.Cingolani

Key ref:

R.A.Pumroy et al. (2015). Molecular determinants for nuclear import of influenza A PB2 by importin α isoforms 3 and 7. Structure, 23, 374-384. PubMed id: 25599645 DOI: 10.1016/j.str.2014.11.015

Date:

08-Aug-14 Release date: 04-Feb-15

Protein chain

P52293  (IMA1_MOUSE) -  Importin subunit alpha-1 from Mus musculus

Seq: 529 a.a.

Struc: 425 a.a.

Protein chain

P31345  (PB2_I75A3) -  Polymerase basic protein 2 from Influenza A virus (strain A/Victoria/3/1975 H3N2)

Seq: 759 a.a.

Struc: 72 a.a.

DOI no: 10.1016/j.str.2014.11.015

Structure 23:374-384 (2015)

PubMed id: 25599645

Molecular determinants for nuclear import of influenza A PB2 by importin α isoforms 3 and 7.

R.A.Pumroy, S.Ke, D.J.Hart, U.Zachariae, G.Cingolani.

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.