Segmental Motions of Proteins under Non-native States Evaluated Using Quasielastic Neutron Scattering

Fujiwara, Satoru; Matsuo, Tatsuhiro; Sugimoto, Yoshiaki; Shibata, Kaoru

doi:10.1021/acs.jpclett.9b03196

Cited by 6 publications

(7 citation statements)

References 35 publications

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“…To date, the QENS method has been used in many studies to characterize the overall picture of protein dynamics 29 . The scope of QENS research is expanding from small single-domain proteins 41,42 to larger and more complex molecular systems 43, 44, , as well as to large-scale conformational changes such as those that occur upon ligand binding 33,46,47 , pressurization 48,49,50 , unfolding 35,51,52,53,54,55 , and fibrillization 34,56 .…”

Section: Discussionmentioning

confidence: 99%

“…(B) Temperature dependences of jump-diffusion frequency (τ -1) for KaiC, human hemoglobin (Hb), and α-synuclein (αSyn). QENS data of Hb and αSyn are taken from previous studies33,51 ; activation energies of deoxygenated Hb (deoxy-Hb), CO-bound Hb (CO-Hb), fibrillized αSyn (fib-αSyn), and monomeric αSyn (mon-αSyn) are 5.2 ± 0.3, 5.2 ± 0.3, 3.7 ± 0.7, and 2.6 ± 1.9 kcal mol -1 , respectively. Values given near fitting lines represent the Q10local values estimated for 303 K.…”

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confidence: 99%

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Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

Furuike

Ouyang²,

Tominaga

et al. 2021

Preprint

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Clock proteins maintain constant enzymatic activity regardless of temperature, even though thermal fluctuation is accelerated as temperature increases. We investigated temperature influences on the dynamics of KaiC, a temperature-compensated ATPase in the cyanobacterial circadian clock system, using quasielastic neutron scattering. The frequency of picosecond to sub-nanosecond incoherent local motions in KaiC was accelerated very slightly in a temperature-dependent manner. Our mutation studies revealed that internal motions of KaiC include several contributions of opposing temperature sensitivities. To take advantage of this balancing effect, the motional frequency of local dynamics in KaiC needs to exceed ∼0.3 ps-1. Some of the mutation sites may be in a pathway through which the motional frequency in the C-terminal domain of KaiC is fed back to the active site of ATPase in its N-terminal domain. The temperature-compensating ability at the dynamics level is likely crucial for circadian clock systems, into which the clock proteins are incorporated, to achieve reaction- or even system-level temperature compensation of the oscillation frequency.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

Furuike

Ouyang²,

Tominaga

et al. 2021

Preprint

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“…Since the convolution of two Lorentzian functions is also a Lorentzian function, fitting the spectra with the equation containing the two Lorentzian functions distinguish the global motions and the local motions. Whereas L global (Q,ω) of well-folded globular proteins contains only the contributions from the diffusive motions as a rigid body, L global (Q, ω) of those containing the disordered regions contains a non-negligible contribution from the segmental motions [15]. In such cases, the QENS spectra can be described as a first approximation that translational and rotational diffusion as a rigid body and the segmental motions are independent of each other, as:…”

Section: Methodsmentioning

confidence: 99%

“…Thus, if the contributions of the diffusive motions of the entire molecules could be estimated, the contributions of the domain/segmental motions should be extracted. We have thus developed an analysis method that can extract motions at the segment/domain level by combining QENS, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) measurements and demonstrated its feasibility [15]. The extraction of the segmental motions is critical for the characterization of the IDPs/IDRs.…”

Section: Introductionmentioning

confidence: 99%

Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering

Fujiwara

2022

Medicina

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Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson’s disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.

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“…Owing to its energy range, high resolution, high intensity, and high S/N, the state-of-the-art NBS instrument is suitable for studying the dynamics of proteins. Using a time-of-flight, near-backscattering spectrometer (BL02), at the Materials and Life Science Experimental Facility at J-PARC, Japan [ 18 ], Fujiwara and Matsuo et al have published studies [ 19 , 20 , 21 , 22 , 23 , 24 ] on protein solutions, including an experiment with the world’s lowest concentration of α-Synuclein at that time (9.5 mg/mL (~0.95 wt.%)) [ 20 ]. In recent years, Inoue et al [ 25 ] and Nakagawa et al [ 26 ] reported studies on protein dynamics within protein solutions.…”

Section: Introductionmentioning

confidence: 99%

Data Collection for Dilute Protein Solutions via a Neutron Backscattering Spectrometer

Tominaga

Sahara

Oda

et al. 2022

Life

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Understanding protein functions requires not only static but also dynamic structural information. Incoherent quasi-elastic neutron scattering (QENS), which utilizes the highly incoherent scattering ability of hydrogen, is a powerful technique for revealing the dynamics of proteins in deuterium oxide (D2O) buffer solutions. The background scattering of sample cells suitable for aqueous protein solution samples, conducted with a neutron backscattering spectrometer, was evaluated. It was found that the scattering intensity of an aluminum sample cell coated with boehmite using D2O was lower than that of a sample cell coated with regular water (H2O). The D2O-Boehmite coated cell was used for the QENS measurement of a 0.8 wt.% aqueous solution of an intrinsically disordered protein in an intrinsically disordered region of a helicase-associated endonuclease for a fork-structured type of DNA. The cell was inert against aqueous samples at 283–363 K. In addition, meticulous attention to cells with small individual weight differences and the positional reproducibility of the sample cell relative to the spectrometer neutron beam position enabled the accurate subtraction of the scattering profiles of the D2O buffer and the sample container. Consequently, high-quality information on protein dynamics could be extracted from dilute protein solutions.

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Segmental Motions of Proteins under Non-native States Evaluated Using Quasielastic Neutron Scattering

Cited by 6 publications

References 35 publications

Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering

Data Collection for Dilute Protein Solutions via a Neutron Backscattering Spectrometer

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