PDBsum entry: 1ial

Nuclear import receptor

PDB id: 1ial

Contents

Protein chain

438 a.a. *

Waters ×179

* Residue conservation analysis

PDB id:

1ial

Name:

Nuclear import receptor

Title:

Importin alpha, mouse

Structure:

Importin alpha. Chain: a. Synonym: karyopherin alpha. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: bl21. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.50Å R-factor: 0.189 R-free: 0.240

Authors:

B.Kobe

Key ref:

B.Kobe (1999). Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha. Nat Struct Biol, 6, 388-397. PubMed id: 10201409 DOI: 10.1038/7625

Date:

12-Jan-99 Release date: 15-Jun-99

Protein chain

P52293  (IMA2_MOUSE) -  Importin subunit alpha-2

Seq: 529 a.a.

Struc: 438 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (3 terms)
• Biological process: intracellular protein transport (2 terms)
• Biochemical function: binding (2 terms)

DOI no: 10.1038/7625

Nat Struct Biol 6:388-397 (1999)

PubMed id: 10201409

Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha.

B.Kobe.

ABSTRACT

Importin alpha is the nuclear import receptor that recognizes classical monopartite and bipartite nuclear localization signals (NLSs). The structure of mouse importin alpha has been determined at 2.5 A resolution. The structure shows a large C-terminal domain containing armadillo repeats, and a less structured N-terminal importin beta-binding domain containing an internal NLS bound to the NLS-binding site. The structure explains the regulatory switch between the cytoplasmic, high-affinity form, and the nuclear, low-affinity form for NLS binding of the nuclear import receptor predicted by the current models of nuclear import. Importin beta conceivably converts the low- to high-affinity form by binding to a site overlapping the autoinhibitory sequence. The structure also has implications for understanding NLS recognition, and the structures of armadillo and HEAT repeats.

Selected figure(s)

Figure 4.
Figure 4. Mechanism of autoinhibition. a, Molecular surface (probe radius 1.4 Å) of the arm repeat domain of importin color-coded according to surface complementarity^49 with the N-terminal segment (residues 44−54). Red, Sc (shape correlation statistic) > 0.76; yellow, 0.76 > Sc > 0.3; green, 0.3 > Sc > -0.3; light blue, Sc < -0.3. The overall Sc equals 0.75. The N-terminal segment is shown in magenta. Drawn with the program GRASP^46. b, Molecular surface of the arm repeat domain of importin color-coded according to electrostatic potential mapped to it. Lys and Arg were assigned a single positive charge, and Glu and Asp were assigned a single negative charge. A uniform dielectric constant of 80 was assumed for the solvent and 2 for the protein interior; the ionic strength was set to zero. Coloring is continuous going from blue (potential +10 kt/e; 1 kt = 0.6 kcal, e is the charge of an electron) through white to red (potential -10 kt/e). The N-terminal segment is shown in magenta. Calculated and drawn with the program GRASP^46. c, Schematic diagram of the interactions between the autoinhibitory segment (residues 44−54) and the arm repeat domain of mouse importin . Polar contacts are shown with dashed lines, and hydrophobic contacts are indicated by arcs with radiating spokes. Atom colors: black, C; medium gray, N; light gray, O. Prepared with the program LIGPLOT^51.

Figure 6.
Figure 6. NLS-binding determinants. a, Schematic diagram of the interactions between the SV40 NLS (S) and yeast Kap 50 at the larger NLS-binding site^21, prepared as Fig. 4c. b, Model of the bipartite NLS from nucleoplasmin (residues 154−173; green) bound to mouse importin (gray ribbon diagram). Although the side chains of all residues of the NLS were used in the modeling, only the side chains occupying P1'−P2' and P1−P4 positions are shown in this figure. Superimposed are the backbones of the autoinhibitory segment of mouse importin (residues 44−45; magenta) and the SV40 NLS bound to the smaller NLS-binding site in yeast Kap 50 (21) after superposition of that structure onto the structure of mouse importin .

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 388-397) copyright 1999.

Figures were selected by an automated process.