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| - | {{STRUCTURE_1w9c| PDB=1w9c | SCENE= }}
| + | ==Proteolytic fragment of CRM1 spanning six C-terminal HEAT repeats== |
| - | ===Proteolytic fragment of CRM1 spanning six C-terminal HEAT repeats===
| + | <StructureSection load='1w9c' size='340' side='right' caption='[[1w9c]], [[Resolution|resolution]] 2.30Å' scene=''> |
| - | {{ABSTRACT_PUBMED_15574331}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1w9c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W9C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W9C FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w9c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1w9c RCSB], [http://www.ebi.ac.uk/pdbsum/1w9c PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w9/1w9c_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase Ran. We present a structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy. The architecture of CRM1 resembles that of the import receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran binding. Residues critical for NES recognition are identified adjacent to the cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We present evidence that a conformational change of the Ran binding loop accounts for the cooperativity of Ran- and substrate binding and for the selective enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate that a single architectural and mechanistic framework can explain the divergent effects of RanGTP on substrate binding by many import and export receptors. |
| | | | |
| - | ==Function==
| + | Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.,Petosa C, Schoehn G, Askjaer P, Bauer U, Moulin M, Steuerwald U, Soler-Lopez M, Baudin F, Mattaj IW, Muller CW Mol Cell. 2004 Dec 3;16(5):761-75. PMID:15574331<ref>PMID:15574331</ref> |
| - | [[http://www.uniprot.org/uniprot/XPO1_HUMAN XPO1_HUMAN]] Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. Several viruses, among them HIV-1, HTLV-1 and influenza A use it to export their unspliced or incompletely spliced RNAs out of the nucleus. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization.<ref>PMID:9323133</ref> <ref>PMID:9311922</ref> <ref>PMID:9837918</ref> <ref>PMID:14612415</ref> <ref>PMID:15574332</ref> <ref>PMID:20921223</ref>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[1w9c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W9C OCA].
| + | </div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | <ref group="xtra">PMID:015574331</ref><references group="xtra"/><references/>
| + | *[[Exportin|Exportin]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | [[Category: Askjaer, P.]] | | [[Category: Askjaer, P.]] |
| Structural highlights
1w9c is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase Ran. We present a structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy. The architecture of CRM1 resembles that of the import receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran binding. Residues critical for NES recognition are identified adjacent to the cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We present evidence that a conformational change of the Ran binding loop accounts for the cooperativity of Ran- and substrate binding and for the selective enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate that a single architectural and mechanistic framework can explain the divergent effects of RanGTP on substrate binding by many import and export receptors.
Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.,Petosa C, Schoehn G, Askjaer P, Bauer U, Moulin M, Steuerwald U, Soler-Lopez M, Baudin F, Mattaj IW, Muller CW Mol Cell. 2004 Dec 3;16(5):761-75. PMID:15574331[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Petosa C, Schoehn G, Askjaer P, Bauer U, Moulin M, Steuerwald U, Soler-Lopez M, Baudin F, Mattaj IW, Muller CW. Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex. Mol Cell. 2004 Dec 3;16(5):761-75. PMID:15574331 doi:10.1016/j.molcel.2004.11.018
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