1qbk: Difference between revisions

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|PDB= 1qbk |SIZE=350|CAPTION= <scene name='initialview01'>1qbk</scene>, resolution 3.0&Aring;
|PDB= 1qbk |SIZE=350|CAPTION= <scene name='initialview01'>1qbk</scene>, resolution 3.0&Aring;
|SITE=  
|SITE=  
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER'>GNP</scene>
|LIGAND= <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
|ACTIVITY=  
|ACTIVITY=  
|GENE=  
|GENE=  
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qbk OCA], [http://www.ebi.ac.uk/pdbsum/1qbk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qbk RCSB]</span>
}}
}}


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==Overview==
==Overview==
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.
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.
==Disease==
Known diseases associated with this structure: Deafness, mitochondrial, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=610230 610230]], Osteolysis, familial expansile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603499 603499]], Paget disease of bone OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603499 603499]]


==About this Structure==
==About this Structure==
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[[Category: Blobel, G.]]
[[Category: Blobel, G.]]
[[Category: Chook, Y M.]]
[[Category: Chook, Y M.]]
[[Category: GNP]]
[[Category: MG]]
[[Category: heat repeat]]
[[Category: heat repeat]]


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