4a4i
From Proteopedia
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| - | [[ | + | ==Crystal structure of the human Lin28b cold shock domain== |
| + | <StructureSection load='4a4i' size='340' side='right' caption='[[4a4i]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4a4i]] 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=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> | ||
| + | </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> | ||
| + | <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='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://www.rcsb.org/pdb/explore.do?structureId=4a4i RCSB], [http://www.ebi.ac.uk/pdbsum/4a4i PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN]] Neuroblastoma. | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:22570413</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | + | ||
| - | == | + | |
| - | < | + | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Doege, N | + | [[Category: Doege, N]] |
| - | [[Category: Heinemann, U | + | [[Category: Heinemann, U]] |
| - | [[Category: Mayr, F | + | [[Category: Mayr, F]] |
| - | [[Category: Schuetz, A | + | [[Category: Schuetz, A]] |
[[Category: Rna binding protein]] | [[Category: Rna binding protein]] | ||
Revision as of 17:39, 25 December 2014
Crystal structure of the human Lin28b cold shock domain
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