2la5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2la5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LA5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2la5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LA5 FirstGlance]. <br>
</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=2la5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2la5 OCA], [https://pdbe.org/2la5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2la5 RCSB], [https://www.ebi.ac.uk/pdbsum/2la5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2la5 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2la5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2la5 OCA], [https://pdbe.org/2la5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2la5 RCSB], [https://www.ebi.ac.uk/pdbsum/2la5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2la5 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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== Function ==
== 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).
[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 ==
We have determined the solution structure of the complex between an arginine-glycine-rich RGG peptide from the human fragile X mental retardation protein (FMRP) and an in vitro-selected guanine-rich (G-rich) sc1 RNA. The bound RNA forms a newly discovered G-quadruplex separated from the flanking duplex stem by a mixed junctional tetrad. The RGG peptide is positioned along the major groove of the RNA duplex, with the G-quadruplex forcing a sharp turn of R(10)GGGGR(15) at the duplex-quadruplex junction. Arg10 and Arg15 form cross-strand specificity-determining intermolecular hydrogen bonds with the major-groove edges of guanines of adjacent Watson-Crick G*C pairs. Filter-binding assays on RNA and peptide mutations identify and validate contributions of peptide-RNA intermolecular contacts and shape complementarity to molecular recognition. These findings on FMRP RGG domain recognition by a combination of G-quadruplex and surrounding RNA sequences have implications for the recognition of other genomic G-rich RNAs.
Structure-function studies of FMRP RGG peptide recognition of an RNA duplex-quadruplex junction.,Phan AT, Kuryavyi V, Darnell JC, Serganov A, Majumdar A, Ilin S, Raslin T, Polonskaia A, Chen C, Clain D, Darnell RB, Patel DJ Nat Struct Mol Biol. 2011 Jun 5;18(7):796-804. doi: 10.1038/nsmb.2064. PMID:21642970<ref>PMID:21642970</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2la5" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 09:54, 1 May 2024

RNA Duplex-Quadruplex Junction Complex with FMRP RGG peptideRNA Duplex-Quadruplex Junction Complex with FMRP RGG peptide

Structural highlights

2la5 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FMR1_HUMAN Defects in FMR1 are the cause of fragile X syndrome (FRAX) [MIM: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.[1] [2] [3] [4] [5] [6] [7] [8] Defects in FMR1 are the cause of fragile X tremor/ataxia syndrome (FXTAS) [MIM: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: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.[9] Defects in FMR1 are the cause of premature ovarian failure syndrome type 1 (POF1) [MIM: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.[10]

Function

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).

References

  1. ↑ Linder B, Plottner O, Kroiss M, Hartmann E, Laggerbauer B, Meister G, Keidel E, Fischer U. Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP. Hum Mol Genet. 2008 Oct 15;17(20):3236-46. doi: 10.1093/hmg/ddn219. Epub 2008 Jul, 28. PMID:18664458 doi:10.1093/hmg/ddn219
  2. ↑ Devys D, Lutz Y, Rouyer N, Bellocq JP, Mandel JL. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet. 1993 Aug;4(4):335-40. PMID:8401578 doi:http://dx.doi.org/10.1038/ng0893-335
  3. ↑ Siomi H, Siomi MC, Nussbaum RL, Dreyfuss G. The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein. Cell. 1993 Jul 30;74(2):291-8. PMID:7688265
  4. ↑ Valverde R, Pozdnyakova I, Kajander T, Venkatraman J, Regan L. Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of fragile X mental retardation protein. Structure. 2007 Sep;15(9):1090-8. PMID:17850748 doi:http://dx.doi.org/10.1016/j.str.2007.06.022
  5. ↑ De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra BA, Willems PJ. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet. 1993 Jan;3(1):31-5. PMID:8490650 doi:http://dx.doi.org/10.1038/ng0193-31
  6. ↑ Verheij C, de Graaff E, Bakker CE, Willemsen R, Willems PJ, Meijer N, Galjaard H, Reuser AJ, Oostra BA, Hoogeveen AT. Characterization of FMR1 proteins isolated from different tissues. Hum Mol Genet. 1995 May;4(5):895-901. PMID:7633450
  7. ↑ Feng Y, Absher D, Eberhart DE, Brown V, Malter HE, Warren ST. FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol Cell. 1997 Dec;1(1):109-18. PMID:9659908
  8. ↑ Darnell JC, Fraser CE, Mostovetsky O, Stefani G, Jones TA, Eddy SR, Darnell RB. Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev. 2005 Apr 15;19(8):903-18. Epub 2005 Apr 1. PMID:15805463 doi:gad.1276805
  9. ↑ Hagerman RJ, Leehey M, Heinrichs W, Tassone F, Wilson R, Hills J, Grigsby J, Gage B, Hagerman PJ. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology. 2001 Jul 10;57(1):127-30. PMID:11445641
  10. ↑ Murray A, Webb J, Grimley S, Conway G, Jacobs P. Studies of FRAXA and FRAXE in women with premature ovarian failure. J Med Genet. 1998 Aug;35(8):637-40. PMID:9719368
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