4ova
From Proteopedia
Structure of the two tandem Tudor domains and a new identified KH0 domain from human Fragile X Mental Retardation Protein
Structural highlights
DiseaseFMR1_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] FunctionFMR1_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 PubMedFlexibility 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
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