4a4i: Difference between revisions

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[[Image:4a4i.png|left|200px]]


{{STRUCTURE_4a4i| PDB=4a4i | SCENE= }}
==Crystal structure of the human Lin28b cold shock domain==
<StructureSection load='4a4i' size='340' side='right'caption='[[4a4i]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</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'>[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>
== Disease ==
[https://www.uniprot.org/uniprot/LN28B_HUMAN LN28B_HUMAN] Neuroblastoma.
== Function ==
[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;">
== 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.


===Crystal structure of the human Lin28b cold shock domain===
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>


{{ABSTRACT_PUBMED_22570413}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 4a4i" style="background-color:#fffaf0;"></div>
[[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].
== References ==
 
<references/>
==Reference==
__TOC__
<ref group="xtra">PMID:022570413</ref><references group="xtra"/>
</StructureSection>
[[Category: Homo sapiens]]
[[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]]
Retrieved from "https://proteopedia.org/4a4i"