View source for 2qnd


==Crystal Structure of the KH1-KH2 domains from human Fragile X Mental Retardation Protein==
<StructureSection load='2qnd' size='340' side='right'caption='[[2qnd]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qnd]] 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=2QND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QND 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2qnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qnd OCA], [https://pdbe.org/2qnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qnd RCSB], [https://www.ebi.ac.uk/pdbsum/2qnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qnd 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).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qn/2qnd_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qnd ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence of Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein.

Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of fragile X mental retardation protein.,Valverde R, Pozdnyakova I, Kajander T, Venkatraman J, Regan L Structure. 2007 Sep;15(9):1090-8. PMID:17850748<ref>PMID:17850748</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2qnd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Regan L]]
[[Category: Valverde R]]