β‐turn formation by a six‐residue linear peptide in solution

Gao, Fengxiao; Li, Y; Yan, Sha; Lai, Luhua; Wang, Y; Wu, Haipeng; Qiu, Yu

doi:10.1034/j.1399-3011.2002.02982.x

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…Previous NMR (29,37) and circular dichroism (29) studies did not identify any secondary structure in the RGG motif. In contrast, circular dichroism and infrared spectroscopy suggested such turns in the RGG box of nucleolin at moderate KCl concentrations (45); however, presented data did not demonstrate all spectral features characteristic for β-turns (46). Although a solid evidence for the formation of β-turns in the unbound RGG box is missing, our structural data clearly shows feasibility of the turn formation in the RGG motif.…”

Section: Discussionmentioning

confidence: 38%

Crystal structure reveals specific recognition of a G-quadruplex RNA by a β-turn in the RGG motif of FMRP

Vasilyev

Polonskaia

Darnell

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

180

181

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Fragile X Mental Retardation Protein (FMRP) is a regulatory RNA binding protein that plays a central role in the development of several human disorders including Fragile X Syndrome (FXS) and autism. FMRP uses an arginine-glycine-rich (RGG) motif for specific interactions with guanine (G)-quadruplexes, mRNA elements implicated in the disease-associated regulation of specific mRNAs. Here we report the 2.8-Å crystal structure of the complex between the human FMRP RGG peptide bound to the in vitro selected G-rich RNA. In this model system, the RNA adopts an intramolecular K + -stabilized G-quadruplex structure composed of three G-quartets and a mixed tetrad connected to an RNA duplex. The RGG peptide specifically binds to the duplex-quadruplex junction, the mixed tetrad, and the duplex region of the RNA through shape complementarity, cation-π interactions, and multiple hydrogen bonds. Many of these interactions critically depend on a type I β-turn, a secondary structure element whose formation was not previously recognized in the RGG motif of FMRP. RNA mutagenesis and footprinting experiments indicate that interactions of the peptide with the duplex-quadruplex junction and the duplex of RNA are equally important for affinity and specificity of the RGG-RNA complex formation. These results suggest that specific binding of cellular RNAs by FMRP may involve hydrogen bonding with RNA duplexes and that RNA duplex recognition can be a characteristic RNA binding feature for RGG motifs in other proteins.R NA-binding proteins (RBPs) control all aspects of RNA metabolism and are fundamental to core cellular processes. ∼14% of identified human RBPs are implicated in a broad spectrum of human pathologies, including neurodegenerative and muscular diseases, metabolic disorders, and cancers (1, 2). Fragile X Mental Retardation Protein (FMRP) is among the most important RBPs because of its central role in several human diseases (3). Loss of FMRP function due to CGG triplet repeat expansion-associated transcriptional silencing or missense mutations in the protein (4, 5) lead to fragile X syndrome (FXS), the most common cause of inherited intellectual disability. Mutations in FMRP are also the leading monogenic cause of autism (6, 7). Intermediate length repeat expansions in the FMR1 gene are linked to fragile X-associated tremor ataxia syndrome (8) and fragile X-associated primary ovarian insufficiency (9).FMRP contains four canonical nucleic acid-binding motifs, three KH domains and one arginine-glycine-rich (RGG) box, which mediate interactions with RNAs in mRNA transport, storage, stability, and regulation of translation (Fig. 1A) (3, 10). Each KH domain has been reported to have a mutation either causing FXS or found in patients with intellectual disability (4, 5, 11). In neurons, FMRP associates with a subset of mRNAs and represses their translation both in the cell body and near synapses (12). Loss of repression of these mRNAs is associated with alterations in synaptic plasticity and dendritic spine dynamics thought to underlie...

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Section: Discussionmentioning

confidence: 38%

Crystal structure reveals specific recognition of a G-quadruplex RNA by a β-turn in the RGG motif of FMRP

Vasilyev

Polonskaia

Darnell

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

180

181

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“…The far UV CD spectra of the native sTNF‐R1 (designated as control) is characterized by a high proportion of β‐turn structure as seen from the weak positive n to π* transition near 220 nm and a strong negative band at around 195 nm due to the π to π* transition 50. This result is corroborated by the infrared spectra of this protein in solution with characteristic bands at 1648, 1668, and 1685 cm −1 (data not shown), characteristic of β‐turn structures 50, 51. The far UV CD spectral signal at around 195 nm is not well defined, due to interference by Cl − ions in this region,52 from NaCl present in the buffer.…”

Section: Resultsmentioning

confidence: 99%

Light-induced aggregation of type I soluble tumor necrosis factor receptor

Roy

Mason

Schöneich

et al. 2009

Journal of Pharmaceutical Sciences

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“…The twist of the hairpin has been suggested in the middle of the molecule near the Gln-Asp residues (Bellet-Amalric et al, 2000). This assumption is supported by the high propensity of asparagine for turn formation which has been established in different model peptides (Dyson et al, 1988(Dyson et al, , 1998Gao et al, 2002;Johnson et al, 1993).…”

Section: Hydration and Orientation Of The Polar Groups Of Dmpcmentioning

confidence: 86%

A Molecular View on the Interaction of the Trojan Peptide Penetratin with the Polar Interface of Lipid Bilayers

Binder

Lindblom

2004

Biophysical Journal

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Penetratin belongs to the family of Trojan peptides that effectively enter cells and therefore can be used as cargoes for agents that are unable to penetrate the cell membrane. We applied polarized infrared spectroscopy in combination with the attenuated total reflection technique to extract information before penetratin binding to lipid membranes with molecular resolution. The amide I band of penetratin in the presence of zwitterionic dimyristoylphosphatidylcholine and of anionic lipid membranes composed of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol shows the characteristics of an antiparallel beta-sheet with a small fraction of turns. Both signatures have been interpreted in terms of a hairpin conformation. The infrared linear dichroism of the amide I band indicates that the peptide chain orients in an oblique fashion whereas the plane of the sheet aligns virtually parallel with respect to the membrane surface. The weak effect of the peptide on dimyristoylphosphatidylcholine gives indication of its superficial binding where the charged lysine and arginine side chains form H-bonds to the phosphate oxygens of the surrounding lipids. The determinants for internalization of penetratin appear to be a peptide sequence with a distribution of positively charged residues along a beta-sheet conformation, which enables the anchoring of the peptide in the polar part of the membranes and the effective compensation of anionic lipid charges.

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β‐turn formation by a six‐residue linear peptide in solution

Cited by 12 publications

References 35 publications

Crystal structure reveals specific recognition of a G-quadruplex RNA by a β-turn in the RGG motif of FMRP

Crystal structure reveals specific recognition of a G-quadruplex RNA by a β-turn in the RGG motif of FMRP

Light-induced aggregation of type I soluble tumor necrosis factor receptor

A Molecular View on the Interaction of the Trojan Peptide Penetratin with the Polar Interface of Lipid Bilayers

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