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5wwz
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the KH2 domain of human RNA-binding E3 ubiquitin-protein ligase MEX-3C== | |
| + | <StructureSection load='5wwz' size='340' side='right' caption='[[5wwz]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5wwz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WWZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">[[5www|5www]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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=5wwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wwz OCA], [http://pdbe.org/5wwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wwz RCSB], [http://www.ebi.ac.uk/pdbsum/5wwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wwz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/MEX3C_HUMAN MEX3C_HUMAN]] Genetic variations in MEX3C may be associated with susceptibility to essential hypertension.<ref>PMID:17015768</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MEX3C_HUMAN MEX3C_HUMAN]] E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation.<ref>PMID:22863774</ref> <ref>PMID:23446422</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | MEX-3 is a KH domain-containing RNA-binding protein, first identified as a translational repressor in Caenorhabditis elegans, while its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3' UTR and posttranscriptional regulation of MEX-3 target transcripts. However, the molecular mechanisms of translational repression and the consensus RNA sequence recognized by the MEX-3C KH domain are unknown. Here, using X-ray crystallography and isothermal titration calorimetry, we investigated the RNA-binding activity and selectivity of human MEX-3C dual KH domains. Our high-resolution crystal structures of individual KH domains complexed with a noncanonical U-rich and a GA-rich RNA sequences revealed that the KH1/2 domains of hMEX-3C bound MRE10, a 10-mer RNA (5'-CAGAGUUUAG-3') consisting of an eight-nucleotide MEX-3-recognition element (MRE) motif, with high affinity. Of note, we also identified a consensus RNA motif recognized by human MEX-3C. The potential RNA-binding sites in the 3' UTR of the human leukocyte antigen serotype (HLA-A2) mRNA were mapped with this RNA-binding motif and were further confirmed by fluorescence polarization. The binding motif identified here will provide valuable information for future investigations of the functional pathways controlled by human MEX-3C and for predicting potential mRNAs regulated by this enzyme. | ||
| - | + | The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3-recognition element (MRE) motif with high affinity.,Yang L, Wang C, Li F, Zhang J, Nayab A, Wu J, Shi Y, Gong Q J Biol Chem. 2017 Aug 14. pii: jbc.M117.797746. doi: 10.1074/jbc.M117.797746. PMID:28808060<ref>PMID:28808060</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5wwz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: RING-type E3 ubiquitin transferase]] | ||
| + | [[Category: Gong, Q]] | ||
| + | [[Category: Li, F]] | ||
| + | [[Category: Wang, C]] | ||
| + | [[Category: Yang, L]] | ||
| + | [[Category: Kh2]] | ||
| + | [[Category: Mex-3c]] | ||
| + | [[Category: Rna binding protein]] | ||
Revision as of 11:02, 24 August 2017
Crystal structure of the KH2 domain of human RNA-binding E3 ubiquitin-protein ligase MEX-3C
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