PMID- 10353245
OWN - NLM
STAT- MEDLINE
DCOM- 19990616
LR  - 20210108
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6733
DP  - 1999 May 20
TI  - Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp.
PG  - 230-7
AB  - Transport factors in the karyopherin-beta (also called importin-beta) family
      mediate the movement of macromolecules in nuclear-cytoplasmic transport pathways.
      Karyopherin-beta2 (transportin) binds a cognate import substrate and targets it
      to the nuclear pore complex. In the nucleus, Ran x GTP binds karyopherin-beta2
      and dissociates the substrate. Here we present the 3.0 A structure of the
      karyopherin-beta2-Ran x GppNHp complex where GppNHp is a non-hydrolysable GTP
      analogue. Karyopherin-beta2 contains eighteen HEAT repeats arranged into two
      continuous orthogonal arches. Ran is clamped in the amino-terminal arch and
      substrate-binding activity is mapped to the carboxy-terminal arch. A large loop
      in HEAT repeat 7 spans both arches. Interactions of the loop with Ran and the
      C-terminal arch implicate it in GTPase-mediated dissociation of the
      import-substrate. Ran x GppNHp in the complex shows extensive structural
      rearrangement, compared to Ran GDP, in regions contacting karyopherin-beta2. This
      provides a structural basis for the specificity of the karyopherin-beta family
      for the GTP-bound state of Ran, as well as a rationale for interactions of the
      karyopherin-Ran complex with the regulatory proteins ranGAP, ranGEF and ranBP1.
FAU - Chook, Y M
AU  - Chook YM
AD  - Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller
      University, New York, New York 10021, USA.
FAU - Blobel, G
AU  - Blobel G
LA  - eng
SI  - PDB/1QBK
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Karyopherins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Recombinant Proteins)
RN  - 34273-04-6 (Guanylyl Imidodiphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.5.2 (ran GTP-Binding Protein)
SB  - IM
CIN - Nature. 1999 May 20;399(6733):208-10. PMID: 10353239
MH  - Amino Acid Sequence
MH  - Biological Transport
MH  - Cell Nucleus/metabolism
MH  - Crystallography, X-Ray
MH  - Escherichia coli
MH  - Guanosine Triphosphate/chemistry/metabolism
MH  - Guanylyl Imidodiphosphate/*chemistry/metabolism
MH  - Humans
MH  - Karyopherins
MH  - Macromolecular Substances
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*chemistry/metabolism
MH  - Protein Conformation
MH  - Receptors, Cytoplasmic and Nuclear/*chemistry/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Repetitive Sequences, Amino Acid
MH  - ran GTP-Binding Protein
EDAT- 1999/06/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/03 10:00
PHST- 1999/06/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/03 10:00 [entrez]
AID - 10.1038/20375 [doi]
PST - ppublish
SO  - Nature. 1999 May 20;399(6733):230-7. doi: 10.1038/20375.