Temperature and solvent dependence of the dynamical landscape of tau protein conformations

Abstract

We report the variation with temperature of the ensemble distribution of conformations spanned by the tau protein in its dynamical states measured by small-angle X-ray scattering (SAXS) using synchrotron radiation. The SAXS data show a clear temperature variation of the distribution of occupied protein conformations from 293 to 318 K. More conformations with a smaller radius of gyration are occupied at higher temperature. The protein-solvent interactions are shown by computer simulation to be essential for controlling the dynamics of protein conformations, providing evidence for the key role of water solvent in the protein dynamics, as proposed by Giorgio Careri.Keywords Protein conformations · Intrinsic disordered proteins · Water effect in conformational landscape · Temperature effects in protein fluctuations

Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer’s disease and other tauopathies

“…Figure 7a-7b displays the processed scattering curves I(s) of two measured tau constructs with both profiles appearing featureless, as expected for a flexible and unstructured peptide. Their flexible nature was also confirmed by the Kratky plot (s 2 I(s) as a function of s) which is traditionally employed to qualitatively identify disordered protein states (Figure 7c-7d , for NH 2 htau and its reverse respectively ) [ 92 , 93 , 95 , 97 , 98 , 99 , 106 ]. As expected, Kratky plots (Figure 7c-7d ) were not bell-shaped with a clearly defined maximum.…”

“…In this context, small angle X-ray scattering (SAXS) is one of the few biophysic approaches which is able to provide detailed structural information on this protein, allowing a quantitative characterization of its conformational polydispersity [ 93 , 94 , 95 ]. Accordingly, the SAXS method has been widely employed in recent years to study the overall structure of both full length tau and its truncated forms [ 95 , 96 , 97 , 98 , 99 , 100 , 101 ] and also to characterize other neuropathologically-relevant small peptides composed of only few tens of residues such as the neurotoxic Aβ1-42 (42 aminoacids) [ 102 ] and the chemically unfolded Angiotensin II (8 aminoacids) [ 103 ]. However, at variance with C-terminal fragments that have been extensively studied [ 95 , 99 , 104 ], very little is known about NH 2 -terminal fragments of tau protein whose structural characterization can provide a better understanding of their potent neurotoxic role [ 13 , 33 , 34 , 105 ].…”

“…For both tau peptides, s 2 I(s) monotonously increased up to reach a plateau at high s values -a behavior which resembleed that of an ideal Gaussian chain [ 106 ]- further confirming their unstructured nature. The gyration radius R G of NH 2 htau and its reverse peptide were then estimated by using the Guinier approximation -according to which the scattering intensity has a Gaussian shape at small s (s<1.3/R G ) [ 92 , 93 , 94 , 95 , 97 , 98 , 99 , 106 ]- and the calculated Guinier plot (lnI(s) vs s 2 ) is reported in Figure 7e-7f respectively. As shown by a linear fit of the data, we obtained R G = 1.32±0.02 nm for NH 2 htau26-44 and 1.23±0.02 nm for its reverse sequence peptide.…”

“…To gain better insights into the overall structure of the two analyzed peptides, we fitted their experimental curves by using the Ensemble Optimization Methods (EOM) implemented in the software package ATSAS [ 92 , 93 , 94 , 95 ], which has been widely used to characterize many intrinsically disordered proteins, including the full length tau and its truncated forms [ 95 , 97 , 98 , 99 ] and the neurotoxic Aβ 1-42 peptide [ 102 ]. The EOM method -starting from the aminoacidic sequence- generates a pool of models spanning the entire chain’s conformational space and then it selects from that pool -by an iterative genetic algorithm- the most probable ensemble of conformations which best fit the experimental data.…”

Correlated Disorder in Myelinated Axons Orientational Geometry and Structure

“…Biological tissues are typically intrinsically heterogeneous; indeed, nowadays new features and properties have been visualized using scanning methods with high spatial resolutions, such as by Atomic Force Microscopy [38][39][40], Confocal Microscopy [40], Scanning Electron Microscopy [35] and Scanning micro X-ray diffraction [15][16][17][18][19][20][21]. Correlated spatial structural fluctuations in biological systems have been correlated with the emergence of quantum coherence in biological matter [35,41], in photosystems [42] and intrinsically disordered proteins [43,44], as well as in lamellar oxides showing quantum coherence [45][46][47][48], where non-Euclidean spatial geometries for signal transmission are able to emerge from a correlated disorder [22,48].…”