2h4m: Difference between revisions

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New page: left|200px<br /> <applet load="2h4m" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h4m, resolution 3.05Å" /> '''Karyopherin Beta2/T...
 
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[[Image:2h4m.gif|left|200px]]<br />
<applet load="2h4m" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2h4m, resolution 3.05&Aring;" />
'''Karyopherin Beta2/Transportin-M9NLS'''<br />


==Overview==
==Karyopherin Beta2/Transportin-M9NLS==
Karyopherinbeta (Kapbeta) proteins bind nuclear localization and export, signals (NLSs and NESs) to mediate nucleocytoplasmic trafficking, a, process regulated by Ran GTPase through its nucleotide cycle. Diversity, and complexity of signals recognized by Kap betas have prevented, prediction of new Kap beta substrates. The structure of Kap beta 2 (also, known as Transportin) bound to one of its substrates, the NLS of hnRNP A1, that we report here explains the mechanism of substrate displacement by, Ran GTPase. Further analyses reveal three rules for NLS recognition by Kap, beta 2: NLSs are structurally disordered in free substrates, have overall, basic character, and possess a central hydrophobic or basic motif followed, by a C-terminal R/H/KX(2-5)PY consensus sequence. We demonstrate the, predictive nature of these rules by identifying NLSs in seven previously, known Kap beta 2 substrates and uncovering 81 new candidate substrates, confirming five experimentally. These studies define and validate a new, NLS that could not be predicted by primary sequence analysis alone.
<StructureSection load='2h4m' size='340' side='right'caption='[[2h4m]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2h4m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H4M FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.05&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h4m OCA], [https://pdbe.org/2h4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h4m RCSB], [https://www.ebi.ac.uk/pdbsum/2h4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h4m ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN] Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref>  The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23455423</ref>
== Function ==
[https://www.uniprot.org/uniprot/ROA1_HUMAN ROA1_HUMAN] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.<ref>PMID:17229681</ref>
== 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/h4/2h4m_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2h4m ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Karyopherinbeta (Kapbeta) proteins bind nuclear localization and export signals (NLSs and NESs) to mediate nucleocytoplasmic trafficking, a process regulated by Ran GTPase through its nucleotide cycle. Diversity and complexity of signals recognized by Kap betas have prevented prediction of new Kap beta substrates. The structure of Kap beta 2 (also known as Transportin) bound to one of its substrates, the NLS of hnRNP A1, that we report here explains the mechanism of substrate displacement by Ran GTPase. Further analyses reveal three rules for NLS recognition by Kap beta 2: NLSs are structurally disordered in free substrates, have overall basic character, and possess a central hydrophobic or basic motif followed by a C-terminal R/H/KX(2-5)PY consensus sequence. We demonstrate the predictive nature of these rules by identifying NLSs in seven previously known Kap beta 2 substrates and uncovering 81 new candidate substrates, confirming five experimentally. These studies define and validate a new NLS that could not be predicted by primary sequence analysis alone.


==Disease==
Rules for nuclear localization sequence recognition by karyopherin beta 2.,Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, Chook YM Cell. 2006 Aug 11;126(3):543-58. PMID:16901787<ref>PMID:16901787</ref>
Known disease associated with this structure: Deafness, mitochondrial, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=610230 610230]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2H4M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H4M OCA].
</div>
<div class="pdbe-citations 2h4m" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Rules for nuclear localization sequence recognition by karyopherin beta 2., Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, Chook YM, Cell. 2006 Aug 11;126(3):543-58. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16901787 16901787]
*[[Importin 3D structures|Importin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Cansizoglu, A.E.]]
[[Category: Cansizoglu AE]]
[[Category: Chook, Y.M.]]
[[Category: Chook YM]]
[[Category: heat repeat]]
[[Category: nuclear import complex]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:26:29 2007''

Latest revision as of 10:39, 9 October 2024

Karyopherin Beta2/Transportin-M9NLSKaryopherin Beta2/Transportin-M9NLS

Structural highlights

2h4m is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.05Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ROA1_HUMAN Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.[1] The disease is caused by mutations affecting the gene represented in this entry.[2]

Function

ROA1_HUMAN Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.[3]

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

Karyopherinbeta (Kapbeta) proteins bind nuclear localization and export signals (NLSs and NESs) to mediate nucleocytoplasmic trafficking, a process regulated by Ran GTPase through its nucleotide cycle. Diversity and complexity of signals recognized by Kap betas have prevented prediction of new Kap beta substrates. The structure of Kap beta 2 (also known as Transportin) bound to one of its substrates, the NLS of hnRNP A1, that we report here explains the mechanism of substrate displacement by Ran GTPase. Further analyses reveal three rules for NLS recognition by Kap beta 2: NLSs are structurally disordered in free substrates, have overall basic character, and possess a central hydrophobic or basic motif followed by a C-terminal R/H/KX(2-5)PY consensus sequence. We demonstrate the predictive nature of these rules by identifying NLSs in seven previously known Kap beta 2 substrates and uncovering 81 new candidate substrates, confirming five experimentally. These studies define and validate a new NLS that could not be predicted by primary sequence analysis alone.

Rules for nuclear localization sequence recognition by karyopherin beta 2.,Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, Chook YM Cell. 2006 Aug 11;126(3):543-58. PMID:16901787[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
  2. ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
  3. ↑ Kim CS, Seol SK, Song OK, Park JH, Jang SK. An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. J Virol. 2007 Apr;81(8):3852-65. Epub 2007 Jan 17. PMID:17229681 doi:http://dx.doi.org/10.1128/JVI.01311-06
  4. ↑ Lee BJ, Cansizoglu AE, Suel KE, Louis TH, Zhang Z, Chook YM. Rules for nuclear localization sequence recognition by karyopherin beta 2. Cell. 2006 Aug 11;126(3):543-58. PMID:16901787 doi:10.1016/j.cell.2006.05.049

2h4m, resolution 3.05Å

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