PDBsum entry 2qna

Transport protein

PDB id: 2qna

Contents

Protein chains

744 a.a. *

30 a.a. *

Ligands

SO4 ×2

Waters ×50

* Residue conservation analysis

PDB id:

2qna

Name:

Transport protein

Title:

Crystal structure of human importin-beta (127-876) in complex with the ibb-domain of snurportin1 (1-65)

Structure:

Importin subunit beta-1. Chain: a. Fragment: residues 127-876. Synonym: karyopherin subunit beta-1, nuclear factor p97, importin 90. Engineered: yes. Snurportin-1. Chain: b. Fragment: residues 1-66. Synonym: RNA u transporter 1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kpnb1, ntf97. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: snupn, rnut1, spn1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.84Å R-factor: 0.235 R-free: 0.282

Authors:

D.Wohlwend,A.Strasser,A.Dickmanns,R.Ficner

Key ref:

D.Wohlwend et al. (2007). Structural Basis for RanGTP Independent Entry of Spliceosomal U snRNPs into the Nucleus. J Mol Biol, 374, 1129-1138. PubMed id: 18028944 DOI: 10.1016/j.jmb.2007.09.065

Date:

18-Jul-07 Release date: 08-Apr-08

Protein chain

Q14974  (IMB1_HUMAN) -  Importin subunit beta-1 from Homo sapiens

Seq: 876 a.a.

Struc: 744 a.a.*

Protein chain

O95149  (SPN1_HUMAN) -  Snurportin-1 from Homo sapiens

Seq: 360 a.a.

Struc: 30 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2007.09.065

J Mol Biol 374:1129-1138 (2007)

PubMed id: 18028944

Structural Basis for RanGTP Independent Entry of Spliceosomal U snRNPs into the Nucleus.

D.Wohlwend, A.Strasser, A.Dickmanns, R.Ficner.

ABSTRACT

The nuclear import of assembled spliceosomal subunits, the uridine-rich small nuclear ribonucleoprotein particles (U snRNPs), is mediated by a nuclear import receptor adaptor couple of importinbeta (Impbeta) and snurportin1 (SPN1). In contrast to any other characterized active nuclear import, the Impbeta/SPN1/U snRNP complex does not require RanGTP for the terminal release from the nuclear basket of the nuclear pore complex (NPC). The crystal structure of Impbeta (127-876) in complex with the Impbeta-binding (IBB) domain of SPN1 (1-65) at 2.8-A resolution reveals that Impbeta adopts an open conformation, which is unique for a functional Impbeta/cargo complex, and rather surprisingly, it resembles the conformation of the Impbeta/RanGTP complex. As binding of RanGTP to Impbeta usually triggers the release of import complexes from the NPC, we propose that by already mimicking a conformation similar to Impbeta/RanGTP the independent dissociation of Impbeta/SPN1 from the nuclear basket is energetically aided.

Selected figure(s)

Figure 1.
Fig. 1. Structure of Impβ in complex with IBB[SPN1]. (a) Overall structure of Impβ/IBB[SPN1], with a view into the C-terminal cavity. The IBB domain of SPN1 is depicted in red, the N-terminal arch of Impβ, which is not involved in the interaction is shown in blue, the C-terminal arch, binding to IBB[SPN1], is shown in green. (b) Structure rotated by 90°, with view from the C terminus of Impβ; colouring as in (a). HEAT 13B, illustrated in yellow, is inclined toward IBB[SPN1]. (c) and (d) Detailed view into interactions between Impβ_127–876 and IBB[SPN1]; colouring as in (a). Side chains involved in binding are depicted as ball and stick presentations. (c) View from the top of the C-terminal arch of Impβ. (d) View from the bottom of the C-terminal arch. (e) and (f) Electron density presentations of the environments of two arginines of IBB[SPN1], which interact with Impβ_127–876. Dotted lines mark hydrogen bonds. (e) The hydrogen bond network with Arg43 of IBB[SPN1] as center involves Cys585, Asp627 and Met630 of Impβ; in close vicinity is Gln40 of IBB[SPN1], forming an intramolecular hydrogen bond. (f) Arg63 not only is bound to Gly820 with a single bond and to Asp824 via a bidentite hydrogen bond, but also coordinates a water molecule that is involved in the hydration shell of Impβ.

Figure 3.
Fig. 3. The overall conformation of Impβ in complex with IBB[SPN1] and IBB[α], respectively, differs significantly. (a) Superposition of the structures of Impβ/IBB[SPN1] (blue) and Impβ/IBB[α] (red). Only Impβ is shown in each case. The superposition reveals a considerable difference of 14 Å in the dilatation of both molecules. The distances between Asn141 and Ala876 were measured and are indicated. (b) Comparison between a homology amino acid sequence alignment^17 and a structure-based sequence alignment of IBB[α] and IBB[SPN1] derived from the crystal structures of Impβ/IBB[α] and Impβ/IBB[SPN1]: Green boxes indicate functionally conserved residues regarding interaction with Impβ; red boxes mark residues of IBB[α] that interact with the acidic loop of Impβ. They also mark the corresponding amino acids of IBB[SPN1] according to Ref. 9.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 374, 1129-1138) copyright 2007.

Figures were selected by an automated process.