4ova

From Proteopedia

(Difference between revisions)

Current revision

Structure of the two tandem Tudor domains and a new identified KH0 domain from human Fragile X Mental Retardation Protein

Structural highlights

4ova is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:
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).

Publication Abstract from PubMed

Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins.

The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers.,Hu Y, Chen Z, Fu Y, He Q, Jiang L, Zheng J, Gao Y, Mei P, Chen Z, Ren X Nat Commun. 2015 Mar 23;6:6634. doi: 10.1038/ncomms7634. PMID:25799254^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Hu Y, Chen Z, Fu Y, He Q, Jiang L, Zheng J, Gao Y, Mei P, Chen Z, Ren X. The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers. Nat Commun. 2015 Mar 23;6:6634. doi: 10.1038/ncomms7634. PMID:25799254 doi:http://dx.doi.org/10.1038/ncomms7634

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ova"

Categories: Homo sapiens | Large Structures | Chen ZH | Chen ZZ

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4ova is ON HOLD  until Paper Publication
+==Structure of the two tandem Tudor domains and a new identified KH0 domain from human Fragile X Mental Retardation Protein==
+<StructureSection load='4ova' size='340' side='right'caption='[[4ova]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ova]] is a 4 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=4OVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OVA 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=4ova FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ova OCA], [https://pdbe.org/4ova PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ova RCSB], [https://www.ebi.ac.uk/pdbsum/4ova PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ova 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 ==
+Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins.
-Authors: Chen, Z.H., Chen, Z.Z.
+The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers.,Hu Y, Chen Z, Fu Y, He Q, Jiang L, Zheng J, Gao Y, Mei P, Chen Z, Ren X Nat Commun. 2015 Mar 23;6:6634. doi: 10.1038/ncomms7634. PMID:25799254<ref>PMID:25799254</ref>
-Description: Structure of the two tandem Tudor domains and a new identified KH0 domain from human Fragile X Mental Retardation Protein
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ova" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chen ZH]]
+[[Category: Chen ZZ]]

4ova

From Proteopedia

Current revision

Structure of the two tandem Tudor domains and a new identified KH0 domain from human Fragile X Mental Retardation Protein

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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