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| | ==Crystal Structure of UP1 Complexed With d(TTAGGGTTA 7GU GG); A Human Telomeric Repeat Containing 7-deaza-guanine== | | ==Crystal Structure of UP1 Complexed With d(TTAGGGTTA 7GU GG); A Human Telomeric Repeat Containing 7-deaza-guanine== |
| - | <StructureSection load='1u1m' size='340' side='right' caption='[[1u1m]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='1u1m' size='340' side='right'caption='[[1u1m]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1u1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U1M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1u1m]] is a 2 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=1U1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U1M FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=7GU:7-DEAZA-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>7GU</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2up1|2up1]], [[1pgz|1pgz]], [[1po6|1po6]], [[1u1k|1u1k]], [[1u1l|1u1l]], [[1u1n|1u1n]], [[1u1o|1u1o]], [[1u1p|1u1p]], [[1u1q|1u1q]], [[1u1r|1u1r]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7GU:7-DEAZA-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>7GU</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNRPA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1u1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u1m OCA], [https://pdbe.org/1u1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u1m RCSB], [https://www.ebi.ac.uk/pdbsum/1u1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u1m ProSAT]</span></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=1u1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1u1m RCSB], [http://www.ebi.ac.uk/pdbsum/1u1m PDBsum]</span></td></tr> | + | </table> |
| - | <table> | + | |
| | == Disease == | | == Disease == |
| - | [[http://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> | + | [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 == | | == Function == |
| - | [[http://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> | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u1/1u1m_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u1/1u1m_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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]. | + | </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=1u1m ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1u1m" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Nucleoprotein|Nucleoprotein]] | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Myers, J C.]] | + | [[Category: Large Structures]] |
| - | [[Category: Shamoo, Y.]] | + | [[Category: Myers JC]] |
| - | [[Category: 7-deaza-guanine]] | + | [[Category: Shamoo Y]] |
| - | [[Category: 7gu]]
| + | |
| - | [[Category: Hnrnp a1]]
| + | |
| - | [[Category: Htr]]
| + | |
| - | [[Category: Human telomeric repeat]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Rna recognition motif]]
| + | |
| - | [[Category: Rrm]]
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| - | [[Category: Transport protein-dna complex]]
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| - | [[Category: Up1]]
| + | |
| Structural highlights
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
Heterogeneous ribonucleoprotein A1 (hnRNP A1) is a prototype for the family of eukaryotic RNA processing proteins containing the common RNA recognition motif (RRM). The region consisting of residues 1-195 of hnRNP A1 is referred to as UP1. This region has two RRMs and has a high affinity for both single-stranded RNA and the human telomeric repeat sequence d(TTAGGG)(n). We have used UP1's novel DNA binding to investigate how RRMs bind nucleic acid bases through their highly conserved RNP consensus sequences. Nine complexes of UP1 bound to modified telomeric repeats were investigated using equilibrium fluorescence binding and X-ray crystallography. In two of the complexes, alteration of a guanine to either 2-aminopurine or nebularine resulted in an increase in K(d) from 88nM to 209nM and 316nM, respectively. The loss of these orienting interactions between UP1 and the substituted base allows it to flip between syn and anti conformations. Substitution of the same base with 7-deaza-guanine preserves the O6/N1 contacts but still increases the K(d) to 296nM and suggests that it is not simply the loss of affinity that gives rise to the base mobility, but also the stereochemistry of the specific contact to O6. Although these studies provide details of UP1 interactions to nucleic acids, three general observations about RRMs are also evident: (1) as suggested by informatic studies, main-chain to base hydrogen bonding makes up an important aspect of ligand recognition (2) steric clashes generated by modification of a hydrogen bond donor-acceptor pair to a donor-donor pair are poorly tolerated and (3) a conserved lysine position proximal to RNP-2 (K(106)-IFVGGI) orients the purine to allow stereochemical discrimination between adenine and guanine based on the 6-position. This single interaction is well-conserved in known RRM structures and appears to be a broad indicator for purine preference in the larger family of RRM proteins.
Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA recognition motif (RRM).,Myers JC, Shamoo Y J Mol Biol. 2004 Sep 17;342(3):743-56. PMID:15342234[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Myers JC, Shamoo Y. Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA recognition motif (RRM). J Mol Biol. 2004 Sep 17;342(3):743-56. PMID:15342234 doi:10.1016/j.jmb.2004.07.029
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