Structure of the nuclear transport complex karyopherin-β2–Ran˙GppNHp

@article{Chook1999StructureOT,
  title={Structure of the nuclear transport complex karyopherin-$\beta$2–Ran˙GppNHp},
  author={Yuh Min Chook and G{\"u}nter Blobel},
  journal={Nature},
  year={1999},
  volume={399},
  pages={230-237}
}
Transport factors in the karyopherin-β (also called importin-β) family mediate the movement of macromolecules in nuclear–cytoplasmic transport pathways. Karyopherin-β2 (transportin) binds a cognate import substrate and targets it to the nuclear pore complex. In the nucleus, Ran˙GTP binds karyopherin-β2 and dissociates the substrate. Here we present the 3.0 Å structure of the karyopherin-β2–Ran˙GppNHp complex where GppNHp is a non-hydrolysable GTP analogue. Karyopherin-β2 contains eighteen HEAT… 
View on Nature
236 Citations
Highly Influential Citations
7
Background Citations
43
Methods Citations
8
Results Citations
1

236 Citations

Citation Type

Citation Type

Structures of importins.
  • E. Conti
  • Biology
    Results and problems in cell differentiation
  • 2002
TLDR
The asymmetric distribution of cytoplasmic RanGDP and nuclear RanGTP drives the directionality of transport processes, ensuring cargo loading and cargo release in the appropriate cell compartments.
On a snailroad to the nucleus
The adoption of a twisted structure of importin-beta is essential for the protein-protein interaction required for nuclear transport.
TLDR
It was found that impbeta449 has a structural similarity with another nuclear migrating protein, namely beta-catenin, which is composed of another type of helix-repeated structure of ARM repeat, and the essential regions for NPC translocation for both importin-beta and beta- catenin are spatially well overlapped with one another.
Recognition of nuclear targeting signals by Karyopherin-β proteins.
Conformational Variability of Nucleo-cytoplasmic Transport Factors*
TLDR
It is revealed that binding of RanGTP/cargo to importin β, transportin, and Xpo-t triggers distinct conformational responses, suggesting that even closely related karyopherins employ different mechanisms of conformational regulation and that cargo and nuclear pore-interacting surfaces of the different receptors may be unique.
Conformational Heterogeneity of Karyopherinβ2 Is Segmental
Karyopherin β2B participates in mRNA export from the nucleus
TLDR
The data support the conclusion that Kap β2B participates directly in the export of a large proportion of cellular mRNAs, and TAP connects Kapβ2B to the m RNAs to be exported.
The Importin β Binding Domain Modulates the Avidity of Importin β for the Nuclear Pore Complex*
TLDR
It is proposed that by controlling the degree of strain in the tertiary structure of importin β, the IBB domain modulates the affinity of the import complex for nucleoporins, thus dictating its persistence inside the NPC.
Structural basis for the nuclear protein import cycle.
  • M. Stewart
  • Biology, Chemistry
    Biochemical Society transactions
  • 2006
TLDR
Crystallography and biochemical and cellular studies have enabled a molecular description of the transport cycle to be developed and tested using protein engineering and computer modelling.
Molecular Basis for the Recognition of Snurportin 1 by Importin β*
TLDR
It is proposed that in vivo the synergy of Nup153 and nuclear RanGTP promotes translocation of uridine-rich ribonucleoproteins into the nucleus.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 50 REFERENCES
Ran-unassisted Nuclear Migration of a 97-kD Component of Nuclear Pore–targeting Complex
TLDR
An examination of the behavior of the β-subunit in living cells and in digitonin-permeabilized cells provides an insight to the yet unsolved question regarding the mechanism by which proteins are directionally transported through the NPC, and the role of Ran in this process.
The Nuclear Transport Factor Karyopherin Binds Stoichiometrically to Ran-GTP and Inhibits the Ran GTPase Activating Protein (*)
TLDR
It is shown here, using all recombinant yeast proteins expressed in Escherichia coli, that karyopherin β binds to Ran-GTP and inhibits GTP hydrolysis stimulated by RanGAP (the Ran-specific GTPase activating protein).
Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins
Role of the Nuclear Transport Factor p10 in Nuclear Import
TLDR
The nuclear import factor p10 appears to coordinate the Ran-dependent association and dissociation reactions underlying nuclear import.
Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta heterodimer by displacing alpha from an overlapping binding site on beta.
TLDR
It is discovered that karyopherin beta's binding site for Ran-GTP shows a striking sequence similarity to the cytoplasmic Ran- GTP binding protein, RanBP1, and it is found that Ran-DTP and kARYopherin alpha bind to overlapping sites on karyophersin beta.
Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta.
TLDR
Data indicate that nuclear import of hnRNP A1 is mediated by a novel cellular import pathway that is distinct from, yet evolutionarily related to, the pathway utilized by basic NLS sequences.
Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form
TLDR
This structure reveals a similarity with the Ras core (G-domain) but with significant variations in regions involved in GDP and Mg2+ coordination (switch I and switch II regions in Ras)9,10, suggesting that there could be major conformational changes upon GTP binding.
Crystallographic Analysis of the Recognition of a Nuclear Localization Signal by the Nuclear Import Factor Karyopherin α
Karyopherin beta2 mediates nuclear import of a mRNA binding protein.
TLDR
Re recombinant beta2 bound directly to recombinant nuclear mRNA-binding protein A1 and inhibited karyopherin alpha/beta1-mediated import of a classical NLS containing substrate and, vice versa, beta1 inhibited beta2- mediated import of A1 substrate, suggesting that the two import pathways merge at the level of docking of beta1 and beta2 to repeat nucleoporins.
Identification of different roles for RanGDP and RanGTP in nuclear protein import.
TLDR
It is shown that nuclear import depends on cytoplasmic RanGDP and free GTP, and that RanGSP binds to the nuclear pore complex (NPC); therefore, import might involve nucleotide exchange and GTP hydrolysis on NPC‐bound Ran.
...
1
2
3
4
5
...