PMID- 18708071
OWN - NLM
STAT- MEDLINE
DCOM- 20081114
LR  - 20211020
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 383
IP  - 4
DP  - 2008 Nov 21
TI  - Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound 
      conformation: implications for nuclear import complex assembly dynamics.
PG  - 772-82
LID - 10.1016/j.jmb.2008.07.090 [doi]
AB  - The asymmetric distribution of the nucleotide-bound state of Ran across the 
      nuclear envelope is crucial for determining the directionality of nuclear 
      transport. In the nucleus, Ran is primarily in the guanosine 5'-triphosphate 
      (GTP)-bound state, whereas in the cytoplasm, Ran is primarily guanosine 
      5'-diphosphate (GDP)-bound. Conformational changes within the Ran switch I and 
      switch II loops are thought to modulate its affinity for importin-beta. Here, we 
      show that RanGDP and importin-beta form a stable complex with a micromolar 
      dissociation constant. This complex can be dissociated by importin-beta binding 
      partners such as importin-alpha. Surprisingly, the crystal structure of the 
      Kap95p-RanGDP complex shows that Kap95p induces the switch I and II regions of 
      RanGDP to adopt a conformation that resembles that of the GTP-bound form. The 
      structure of the complex provides insights into the structural basis for the 
      gradation of affinities regulating nuclear protein transport.
FAU - Forwood, Jade K
AU  - Forwood JK
AD  - School of Biomedical Sciences, Charles Sturt University, Wagga Wagga 2650, 
      Australia. jforwood@csu.edu.au
FAU - Lonhienne, Thierry G
AU  - Lonhienne TG
FAU - Marfori, Mary
AU  - Marfori M
FAU - Robin, Gautier
AU  - Robin G
FAU - Meng, Weining
AU  - Meng W
FAU - Guncar, Gregor
AU  - Guncar G
FAU - Liu, Sai M
AU  - Liu SM
FAU - Stewart, Murray
AU  - Stewart M
FAU - Carroll, Bernard J
AU  - Carroll BJ
FAU - Kobe, Bostjan
AU  - Kobe B
LA  - eng
SI  - PDB/3EA5
GR  - MC_U105178939/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080807
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (beta Karyopherins)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - EC 3.6.5.2 (ran GTP-Binding Protein)
SB  - IM
MH  - Active Transport, Cell Nucleus/*physiology
MH  - Amino Acid Sequence
MH  - Crystallography, X-Ray
MH  - Guanosine Diphosphate/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Multiprotein Complexes/chemistry/metabolism
MH  - Protein Binding
MH  - *Protein Conformation
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism
MH  - Sequence Alignment
MH  - beta Karyopherins/*chemistry/genetics/*metabolism
MH  - ran GTP-Binding Protein/*chemistry/genetics/*metabolism
EDAT- 2008/08/19 09:00
MHDA- 2008/11/15 09:00
CRDT- 2008/08/19 09:00
PHST- 2008/03/25 00:00 [received]
PHST- 2008/07/31 00:00 [revised]
PHST- 2008/07/31 00:00 [accepted]
PHST- 2008/08/19 09:00 [pubmed]
PHST- 2008/11/15 09:00 [medline]
PHST- 2008/08/19 09:00 [entrez]
AID - S0022-2836(08)00970-4 [pii]
AID - 10.1016/j.jmb.2008.07.090 [doi]
PST - ppublish
SO  - J Mol Biol. 2008 Nov 21;383(4):772-82. doi: 10.1016/j.jmb.2008.07.090. Epub 2008 
      Aug 7.