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| | ==Crystal structure of the human Lin28b cold shock domain== | | ==Crystal structure of the human Lin28b cold shock domain== |
| - | <StructureSection load='4a4i' size='340' side='right' caption='[[4a4i]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4a4i' size='340' side='right'caption='[[4a4i]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4a4i]] 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=4A4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A4I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4a4i]] 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=4A4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A4I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a65|4a65]], [[4a76|4a76]], [[4alp|4alp]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a4i OCA], [http://pdbe.org/4a4i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a4i RCSB], [http://www.ebi.ac.uk/pdbsum/4a4i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a4i ProSAT]</span></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=4a4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a4i OCA], [https://pdbe.org/4a4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a4i RCSB], [https://www.ebi.ac.uk/pdbsum/4a4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a4i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN]] Neuroblastoma. | + | [https://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN] Neuroblastoma. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN]] Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let-7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation. Mediates MYC-mediated let-7 repression. Isoform 1, when overexpressed, stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.<ref>PMID:16971064</ref> <ref>PMID:18951094</ref> <ref>PMID:19703396</ref> | + | [https://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN] Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let-7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation. Mediates MYC-mediated let-7 repression. Isoform 1, when overexpressed, stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.<ref>PMID:16971064</ref> <ref>PMID:18951094</ref> <ref>PMID:19703396</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Doege, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Heinemann, U]] | + | [[Category: Doege N]] |
| - | [[Category: Mayr, F]] | + | [[Category: Heinemann U]] |
| - | [[Category: Schuetz, A]] | + | [[Category: Mayr F]] |
| - | [[Category: Rna binding protein]]
| + | [[Category: Schuetz A]] |
| Structural highlights
Disease
LN28B_HUMAN Neuroblastoma.
Function
LN28B_HUMAN Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let-7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation. Mediates MYC-mediated let-7 repression. Isoform 1, when overexpressed, stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.[1] [2] [3]
Publication Abstract from PubMed
The RNA-binding protein Lin28 regulates the processing of a developmentally important group of microRNAs, the let-7 family. Lin28 blocks the biogenesis of let-7 in embryonic stem cells and thereby prevents differentiation. It was shown that both RNA-binding domains (RBDs) of this protein, the cold-shock domain (CSD) and the zinc-knuckle domain (ZKD) are indispensable for pri- or pre-let-7 binding and blocking its maturation. Here, we systematically examined the nucleic acid-binding preferences of the Lin28 RBDs and determined the crystal structure of the Lin28 CSD in the absence and presence of nucleic acids. Both RNA-binding domains bind to single-stranded nucleic acids with the ZKD mediating specific binding to a conserved GGAG motif and the CSD showing only limited sequence specificity. However, only the isolated Lin28 CSD, but not the ZKD, can bind with a reasonable affinity to pre-let-7 and thus is able to remodel the terminal loop of pre-let-7 including the Dicer cleavage site. Further mutagenesis studies reveal that the Lin28 CSD induces a conformational change in the terminal loop of pre-let-7 and thereby facilitates a subsequent specific binding of the Lin28 ZKD to the conserved GGAG motif.
The Lin28 cold-shock domain remodels pre-let-7 microRNA.,Mayr F, Schutz A, Doge N, Heinemann U Nucleic Acids Res. 2012 May 8. PMID:22570413[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T, Aburatani H. Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene. 2006 Dec 15;384:51-61. Epub 2006 Jul 28. PMID:16971064 doi:http://dx.doi.org/S0378-1119(06)00444-6
- ↑ Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell. 2008 Oct 24;32(2):276-84. doi: 10.1016/j.molcel.2008.09.014. PMID:18951094 doi:http://dx.doi.org/10.1016/j.molcel.2008.09.014
- ↑ Heo I, Joo C, Kim YK, Ha M, Yoon MJ, Cho J, Yeom KH, Han J, Kim VN. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009 Aug 21;138(4):696-708. doi: 10.1016/j.cell.2009.08.002. PMID:19703396 doi:http://dx.doi.org/10.1016/j.cell.2009.08.002
- ↑ Mayr F, Schutz A, Doge N, Heinemann U. The Lin28 cold-shock domain remodels pre-let-7 microRNA. Nucleic Acids Res. 2012 May 8. PMID:22570413 doi:10.1093/nar/gks355
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