View source for 4qvz


==FMRP N-terminal domain==
<StructureSection load='4qvz' size='340' side='right'caption='[[4qvz]], [[Resolution|resolution]] 3.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qvz]] 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=4QVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QVZ 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]] 3.195&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4qvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qvz OCA], [https://pdbe.org/4qvz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qvz RCSB], [https://www.ebi.ac.uk/pdbsum/4qvz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qvz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FMR1_HUMAN FMR1_HUMAN] Defects in FMR1 are the cause of fragile X syndrome (FRAX) [MIM:[https://omim.org/entry/300624 300624]. Fragile X syndrome is a common genetic disease (has a prevalence of one in every 2000 children) which is characterized by moderate to severe mental retardation, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most fragile X syndrome patients results from an amplification of a CGG repeat region which is directly in front of the coding region.<ref>PMID:18664458</ref> <ref>PMID:8401578</ref> <ref>PMID:7688265</ref> <ref>PMID:17850748</ref> <ref>PMID:8490650</ref> <ref>PMID:7633450</ref> <ref>PMID:9659908</ref> <ref>PMID:15805463</ref>   Defects in FMR1 are the cause of fragile X tremor/ataxia syndrome (FXTAS) [MIM:[https://omim.org/entry/300623 300623]. In FXTAS, the expanded repeats range in size from 55 to 200 repeats and are referred to as 'premutations'. Full repeat expansions with greater than 200 repeats results in fragile X mental retardation syndrome [MIM:[https://omim.org/entry/300624 300624]. Carriers of the premutation typically do not show the full fragile X syndrome phenotype, but comprise a subgroup that may have some physical features of fragile X syndrome or mild cognitive and emotional problems.<ref>PMID:11445641</ref>   Defects in FMR1 are the cause of premature ovarian failure syndrome type 1 (POF1) [MIM:[https://omim.org/entry/311360 311360]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:9719368</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FMR1_HUMAN FMR1_HUMAN] Translation repressor. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates translation repression (By similarity). RNA-binding protein that plays a role in intracellular RNA transport and in the regulation of translation of target mRNAs. Associated with polysomes. May play a role in the transport of mRNA from the nucleus to the cytoplasm. Binds strongly to poly(G), binds moderately to poly(U) but shows very little binding to poly(A) or poly(C).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, FMRP. FMRP is a selective RNA-binding protein owing to two central KH domains and a C-terminal RGG box. However, several properties of the FMRP amino terminus are unresolved. It has been documented for over a decade that the amino terminus has the ability to bind RNA despite having no recognizable functional motifs. Moreover, the amino terminus has recently been shown to bind chromatin and influence the DNA damage response as well as function in the presynaptic space, modulating action potential duration. We report here the amino terminal crystal structures of wild-type FMRP, and a mutant (R138Q) that disrupts the amino terminus function, containing an integral tandem Agenet and discover a novel KH motif.

Human FMRP contains an integral tandem Agenet (Tudor) and KH motif in the amino terminal domain.,Myrick LK, Hashimoto H, Cheng X, Warren ST Hum Mol Genet. 2014 Nov 20. pii: ddu586. PMID:25416280<ref>PMID:25416280</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qvz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng X]]
[[Category: Hashimoto H]]
[[Category: Myrick LK]]
[[Category: Warren ST]]