Conformational Prerequisites for Formation of Amyloid Fibrils from Histones

Munishkina, Larissa A.; Fink, Anthony L.; Uversky, Vladimir N.

doi:10.1016/j.jmb.2004.06.094

Cited by 74 publications

(77 citation statements)

References 92 publications

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“…The spectra of the folded tetramer and fibrils in Figure 4 are similar to those that have been reported previously for a mixture of calf thymus histones. 11 The spectra of the fibrils from individual H3 and H4 histones are quite similar to each other. In contrast, the fibrils from unfolded H3 þ H4 and from folded tetramer have different ratios of the 1645 cm À1 and 1625 cm À1 maxima, suggesting there may be subtle differences in the fibrillar structure or the segments of protein not incorporated into the cross-b fibril structure.…”

Section: Characterization Of the Histone Fibrils By Different Methodsmentioning

confidence: 73%

“…43 At comparable conditions, the T M values for hMfB and hPyA1 are >80 C. 44 Various reports have shown that histones are stabilized by increasing ionic strength. 11,41,42,44,45 Yet, decreasing ionic strength (thus stability) did not facilitate fibrillation of hMfB, hPyA1, or H2A þ H2B (Supporting Information Table S1) and impeded the fibrillation of H3-H4 (see below). A similar lack of correlation between stability and fibrillation was observed with wild-type and chimeric human stefins.…”

Section: Fibrillation Propensity Of Different Histonesmentioning

confidence: 98%

“…The previously published studies using calf thymus core histones 11 served as a guide in choosing conditions to screen for fibril formation: pH 2 and pH 5 with 1M NaCl at room temperature. In these solvent conditions (at 37 C), fibrillation of the bovine histone mixture was detected within 24 h and complete by 60 h. In the current study, the propensity of individual recombinant histones to form fibrils was assessed by starting with histone monomers unfolded in 10 mM HCl with rapid dilution into fibrillation conditions.…”

Section: Fibrillation Propensity Of Different Histonesmentioning

confidence: 99%

“…In contrast to the high sequence divergence between the four eukaryotic histones, the individual histones exhibit high sequence identity across species. For example, the H3 histones of Xenopus laevis, used in this study, bovine (used in a previous study of fibrillation) 11 and humans are 98% identical, with two differences in 135 residues, and the H4 histones from the three species are identical across 102 residues.…”

mentioning

confidence: 99%

“…12,14,15 Previous studies have shown that eukaryotic histones can form amyloid-like fibrils. 11,39 These fibrillation studies used a mixture of calf thymus histones containing H2A, H2B, H3, and H4. Thus, the fibrillation propensity of the individual histone sequences was not assessed.…”

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confidence: 99%

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The impact of solubility and electrostatics on fibril formation by the H3 and H4 histones

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2011

Protein Science

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The goal of this study was to examine fibril formation by the heterodimeric eukaryotic histones (H2A-H2B and H3-H4) and homodimeric archaeal histones (hMfB and hPyA1). The histone fold dimerization motif is an obligatorily domain-swapped structure comprised of two fused helix:b-loop:helix motifs. Domain swapping has been proposed as a mechanism for the evolution of protein oligomers as well as a means to form precursors in the formation of amyloid-like fibrils. Despite sharing a common fold, the eukaryotic histones of the core nucleosome and archaeal histones fold by kinetic mechanisms of differing complexity with transient population of partially folded monomeric and/or dimeric species. No relationship was apparent between fibrillation propensity and equilibrium stability or population of kinetic intermediates. Only H3 and H4, as isolated monomers and as a heterodimer, readily formed fibrils at room temperature, and this propensity correlates with the significantly lower solubility of these polypeptides. The fibrils were characterized by ThT fluorescence, FTIR, and far-UV CD spectroscopies and electron microscopy. The helical histone fold comprises the protease-resistant core of the fibrils, with little or no protease protection of the poorly structured N-terminal tails. The highly charged tails inhibit fibrillation through electrostatic repulsion. Kinetic studies indicate that H3 and H4 form a co-fibril, with simultaneous incorporation of both histones. The potential impact of H3 and H4 fibrillation on the cytotoxicity of extracellular histones and a-synuclein-mediated neurotoxicity and fibrillation is considered.

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Section: Characterization Of the Histone Fibrils By Different Methodsmentioning

confidence: 73%

Section: Fibrillation Propensity Of Different Histonesmentioning

confidence: 98%

Section: Fibrillation Propensity Of Different Histonesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The impact of solubility and electrostatics on fibril formation by the H3 and H4 histones

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2011

Protein Science

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Structural Insights into Intrinsically Disordered Proteins by Small‐Angle X‐Ray Scattering

Bernadó

Svergun

2010

Instrumental Analysis of Intrinsically Disordered Proteins

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16Small -angle X -ray scattering (SAXS) is widely employed to study the overall solution structure and structural transitions of folded biologic macromolecules. At the same time, SAXS is one of the very few techniques yielding structural information about fl exible macromolecules, unfolded and intrinsically unfolded proteins. In the past, SAXS was more often employed to qualitatively monitor the folding/unfolding processes by a few overall parameters; modern modeling methods allow one to extract much more detailed quantitative information for a better understanding of the biologic role of these proteins. In this chapter, after a brief introduction to the technical and experimental details of SAXS, its applications to the IDPs are described. Classical approaches based on the analysis of overall parameters are presented, and a recent development, the ensemble optimization method, is also explained in detail. The latter approach takes the conformational plasticity of IDPs into account by allowing for coexistence of multiple protein conformations in solution, and the analysis of the ensembles provides a new source of structural information. ABSTRACT 452 INSTRUMENTAL ANALYSIS OF INTRINSICALLY DISORDERED PROTEINSThis approach and the combination of SAXS with other biophysical techniques, such as NMR, Föster Resonance Energy Transfer (FRET) , and molecular simulations, promise structural insights into the detection of structural disorder and into monitoring of structural perturbations of IDPs upon environmental changes or binding to biologic partners.

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