5nvm: Difference between revisions

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-'''Unreleased structure'''
-The entry 5nvm is ON HOLD
+==Crystal structure of the human 4EHP-GIGYF2 complex lacking the auxiliary sequences==
+<StructureSection load='5nvm' size='340' side='right' caption='[[5nvm]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5nvm]] is a 4 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=5NVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NVM FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF4E2, EIF4EL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GIGYF2, KIAA0642, PERQ2, TNRC15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5nvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nvm OCA], [http://pdbe.org/5nvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nvm RCSB], [http://www.ebi.ac.uk/pdbsum/5nvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nvm ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/GGYF2_HUMAN GGYF2_HUMAN]] Young adult-onset Parkinsonism. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Its association with Parkinson disease is however unclear. According to a number of studies, variations affecting this gene are not a frequent cause of Parkinson disease, suggesting that GIGYF2 does not play a major role in Parkinson disease etiology (PubMed:19279319, PubMed:19429085, PubMed:19638301, PubMed:19482505, PubMed:20004041, PubMed:19321232, PubMed:20060621).<ref>PMID:19279319</ref> <ref>PMID:19321232</ref> <ref>PMID:19429085</ref> <ref>PMID:19482505</ref> <ref>PMID:19638301</ref> <ref>PMID:20004041</ref> <ref>PMID:20060621</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/IF4E2_HUMAN IF4E2_HUMAN]] Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).[UniProtKB:Q8BMB3]<ref>PMID:17368478</ref> <ref>PMID:22751931</ref> <ref>PMID:25624349</ref> <ref>PMID:9582349</ref>  [[http://www.uniprot.org/uniprot/GGYF2_HUMAN GGYF2_HUMAN]] Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931). In 4EHP-GYF2 the complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (By similarity). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153).[UniProtKB:Q6Y7W8]<ref>PMID:12771153</ref> <ref>PMID:22751931</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5' cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP-GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.
-Authors:
+GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.,Peter D, Weber R, Sandmeir F, Wohlbold L, Helms S, Bawankar P, Valkov E, Igreja C, Izaurralde E Genes Dev. 2017 Jun 1;31(11):1147-1161. doi: 10.1101/gad.299420.117. Epub 2017, Jul 11. PMID:28698298<ref>PMID:28698298</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5nvm" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Peter, D]]
+[[Category: Valkov, E]]
+[[Category: 4ehp-binding protein]]
+[[Category: Cap-binding protein]]
+[[Category: Grb10-interacting gyf protein 2]]
+[[Category: Translation]]
+[[Category: Translational regulation]]