Conformational Analysis of LYS(11−36), a Peptide Derived from the β-Sheet Region of T4 Lysozyme, in TFE and SDS

Najbar, Lidia V.; Craik, David J.; Wade, John D.; Salvatore, Daniella; McLeish, Michael J.

doi:10.1021/bi970730s

Cited by 48 publications

(41 citation statements)

References 66 publications

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“…At intermediate TFE concentrations, the spectra indicate β-structure. These spectra are similar to those obtained by Najbar et al (1997) at pH 4.8 in 10-mM potassium phosphate buffer.…”

Section: Association Constant and Potential Of Mean Forcesupporting

confidence: 84%

“…At intermediate TFE concentrations, the spectra indicate β-structure. These spectra are similar to those obtained by Najbar et al (1997) at pH 4.8 in 10-mM potassium phosphate buffer.Figure 5 also shows fits for the spectra using the reference data set of Brahms and Brahms (1980). Figure 6 shows the extent of secondary structure obtained from these fitted spectra.…”

supporting

confidence: 84%

“…In general, TFE is used to denature proteins and to stabilize secondary structures in peptides. In aqueous solutions containing increasing TFE concentrations, T4 LYS(11-36) has been shown to undergo a secondary-structure transition from random coil to β-sheet to α-helix (Najbar et al, 1997). Because the secondary structure of a peptide can play a role in intermolecular interactions, the secondary structure of T4 LYS(11-36) is determined from circular-dichroism (CD) spectropolarimetry in solution conditions similar to those used for fluorescence-anisotropy measurements.…”

mentioning

confidence: 99%

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Effect of secondary structure on the interactions of peptide T4 LYS (11-36) in mixtures of aqueous sodium chloride and 2,2,2,-Trifluoroethanol

Anderson¹,

Spiegelberg²,

Prausnitz³

et al. 2001

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Note: Tables 3 and 4 are camera-ready.A diskette of the manuscript is included. Text saved in Microsoft Word for PC. AbstractThe potential of mean force for protein-protein interactions is key to the development of a statistical-mechanical model for salt-induced protein precipitation and crystallization, and for understanding certain disease states, including cataract formation and β-amyloid pathology in Alzheimer's disease. Fluorescence anisotropy provides a method for quantitative characterization of intermolecular interactions due to reversible association. Monomer-dimer equilibria for the peptide T4 LYS(11-36) were studied by fluorescence anisotropy. This peptide, derived from the β-sheet region of the T4 lysozyme molecule, has the potential to form amyloid fibrils. 2,2,2-trifluoroethanol (TFE) induces a change in peptide secondary structure, and was used in aqueous solutions at concentrations from 0 to 50% (v/v) at 25 and 37 o C to examine the role of peptide conformation on peptide-peptide interactions. The association constant for dimerization increased with rising TFE concentration and with falling temperature. The peptide-peptide potential of mean force was computed from these association constants. Circular-dichroism measurements showed that the secondary structure of the peptide plays an important role in these strong attractive interactions due to intermolecular hydrogen-bond formation and hydrophobic interactions.Keywords: Protein-protein interactions; 2,2,2-trifluoroethanol; Potential of mean force; Fluorescence polarization; Fluorescence anisotropy; Amyloid fibrillogenesis; Circular dichroism; Secondary structure.Anderson et al., 1Protein-protein interactions can be selectively enhanced to precipitate target proteins from fermentation processes and to crystallize proteins for characterization by X-ray diffraction.Optimized conditions for salt-induced protein precipitation and crystallization have typically been identified on a trial-and-error basis or through empirical correlations. Through measurements of protein-protein interactions under dilute-solution conditions, a molecularthermodynamic model can be developed for predicting selective phase separation of proteins in aqueous electrolyte solutions.Strongly attractive intermolecular interactions between proteins lead to a variety of disease states. The neurotoxicity in Alzheimer's disease has been hypothesized to arise from the association of monomers or dimers of Aβ protein to form protofibrils with β-sheet structure (Walsh et al., 1997;Harper et al., 1997;Shen and Murphy, 1995). These protofibrils lengthen to fibrils that form clusters. Amyloid plaques are observed in the brains of Alzheimer's victims.Human diseases that involve similar pathology include type II diabetes, hereditary systemic amyloidosis and Creutzfeldt-Jakob disease. Therefore, quantitative characterization of the intermolecular forces that produce protein aggregation may lead to a better understanding of the origin of these diseases.This work is concerned with protein-protein...

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“…At intermediate TFE concentrations, the spectra indicate β-structure. These spectra are similar to those obtained by Najbar et al (1997) at pH 4.8 in 10-mM potassium phosphate buffer.…”

Section: Association Constant and Potential Of Mean Forcesupporting

confidence: 84%

supporting

confidence: 84%

mentioning

confidence: 99%

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Effect of secondary structure on the interactions of peptide T4 LYS (11-36) in mixtures of aqueous sodium chloride and 2,2,2,-Trifluoroethanol

Anderson¹,

Spiegelberg²,

Prausnitz³

et al. 2001

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“…For example, extensive use of the fragment dissection approach has been made to determine nucleation sites for the folding of T4 lysozyme (34,35). In that case it was found that peptide fragments corresponding to helical regions in the intact protein generally had an intrinsic tendency to be helical in the isolated fragments, but this was not the case for β-sheet regions.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin

Wilce¹,

Daly²,

Craik³

2002

Clinical Chemistry and Laboratory Medicine

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Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and retinol in human serum. Misfolded forms of the protein are implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. Its folding properties and stabilization by ligands are of current interest due to their importance in understanding and combating these diseases. To assist in such studies we developed a method for the solid phase synthesis of the monomeric unit of a TTR analogue and its folding to form a functional 55 kDa tetramer. The monomeric unit of the protein was chemically synthesized in three parts, comprising amino acid residues 1 -51, 54 -99 and 102 -127, and ligated using chemoselective thioether ligation chemistry. The synthetic protein was folded and assembled to a tetrameric structure in the presence of the TTR's native ligand, thyroxine, as shown by gel filtration chromatography, native gel electrophoresis, TTR antibody recognition and thyroid hormone binding. In the current study the solution structure of the first of these fragment peptides, TTR(1 -51) is examined to determine its intrinsic propensity to form ␤-sheet structure, potentially involved in amyloid fibril formation by TTR. Despite the presence of extensive ␤-structure in the native form of the protein, the N-terminal fragment adopts an essentially random coil conformation in solution.

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“…However, several peptides, mostly exceeding 50 amino acid residues, have nonhelical structures such as the C-␥ phorbol-binding domain (193), sapecin (194), leucocin A (195), epidermal growth factor (25), and tritrpticin (196). Some peptides show dramatically different structures depending on the lipidlike environment used (197,198). Others, such as gramicidin (199), bacterioopsin (121), fd bacteriophage coat protein (200), melittin (96), M2 channel peptides (201), and a myristoylated ARF-1 peptide (202) show little or no structural change (12).…”

Section: Structure Generation and Analysismentioning

confidence: 99%

Structure Determination of Membrane-Associated Proteins from Nuclear Magnetic Resonance Data

Baleja

2001

Analytical Biochemistry

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Conformational Analysis of LYS(11−36), a Peptide Derived from the β-Sheet Region of T4 Lysozyme, in TFE and SDS

Cited by 48 publications

References 66 publications

Effect of secondary structure on the interactions of peptide T4 LYS (11-36) in mixtures of aqueous sodium chloride and 2,2,2,-Trifluoroethanol

Effect of secondary structure on the interactions of peptide T4 LYS (11-36) in mixtures of aqueous sodium chloride and 2,2,2,-Trifluoroethanol

Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin

Structure Determination of Membrane-Associated Proteins from Nuclear Magnetic Resonance Data

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