scholarly journals NMR Relaxation in Proteins with Fast Internal Motions and Slow Conformational Exchange: Model-Free Framework and Markov State Simulations

2013 ◽  
Vol 117 (22) ◽  
pp. 6625-6634 ◽  
Author(s):  
Junchao Xia ◽  
Nan-jie Deng ◽  
Ronald M. Levy
Keyword(s):  
Nmr Relaxation ◽  
Exchange Model ◽  
Conformational Exchange ◽  
Markov State ◽  
Model Free ◽  
Internal Motions

Global and internal molecular dynamics of poly(acrylamide-co-allyl 2-acetamido-2-deoxy-D-glucopyranoside) glycopolymers from 13C NMR relaxation studies

1993 ◽  
Vol 71 (12) ◽  
pp. 1995-2006 ◽  
Author(s):  
René Roy ◽  
François D. Tropper ◽  
Antony J. Williams ◽  
Jean-Robert Brisson
Keyword(s):  
Molecular Dynamics ◽  
Spin Relaxation ◽  
Correlation Time ◽  
Relaxation Times ◽  
Nmr Relaxation ◽  
Relaxation Rates ◽  
Polymer Backbone ◽  
Model Free ◽  
Internal Motions ◽  
Poly Acrylamide

13C spin-lattice and spin–spin relaxation times and nuclear Overhauser enhancements have been used to examine the molecular dynamics of the α- (1) and β- (2) anomeric forms of poly(acrylamide-co-allyl 2-acetamido-2-deoxy-D-glucopyranoside) glycopolymers. The timescale of motions and the spatial restriction of these motions were determined by using various forms of the "model-free" approach. It is shown that the motions of the C—H vectors of the polymer backbone may be described by a scaled Lorentzian spectral density function, giving rise to an effective correlation time for overall tumbling. The temperature dependence of this correlation time suggests that the overall motion is dependent on viscosity. The overall motion of the polymer molecules is shown to be anisotropic in nature by including the spin–spin relaxation data in the analysis. The N-acetyl methyl and sugar hydroxymethyl (C6) groups exhibit internal motions. The activation energies associated with these internal motions are derived. The difference in relaxation rates between the α and β anomeric forms, though small, suggests that the motions of the sugar ring may be different for the two systems. This conclusion is supported by potential energy contour map calculations, which indicate that the β anomer (2) has almost twice the conformational flexibility of the α anomer (1).

scholarly journals Analysis of Artifacts Caused by Pulse Imperfections in CPMG Pulse Trains in NMR Relaxation Dispersion Experiments

2018 ◽  
Vol 4 (3) ◽  
pp. 33 ◽  
Author(s):  
Tsuyoshi Konuma ◽  
Aritaka Nagadoi ◽  
Jun-ichi Kurita ◽  
Takahisa Ikegami
Keyword(s):  
Dipolar Coupling ◽  
Residual Dipolar Coupling ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Resonance Effects ◽  
Pulse Trains ◽  
At Resonance ◽  
Selective Inversion ◽  
Resonance Relaxation

Nuclear magnetic resonance relaxation dispersion (rd) experiments provide kinetics and thermodynamics information of molecules undergoing conformational exchange. Rd experiments often use a Carr-Purcell-Meiboom-Gill (CPMG) pulse train equally separated by a spin-state selective inversion element (U-element). Even with measurement parameters carefully set, however, parts of 1H–15N correlations sometimes exhibit large artifacts that may hamper the subsequent analyses. We analyzed such artifacts with a combination of NMR measurements and simulation. We found that particularly the lowest CPMG frequency (νcpmg) can also introduce large artifacts into amide 1H–15N and aromatic 1H–13C correlations whose 15N/13C resonances are very close to the carrier frequencies. The simulation showed that the off-resonance effects and miscalibration of the CPMG π pulses generate artifact maxima at resonance offsets of even and odd multiples of νcpmg, respectively. We demonstrate that a method once introduced into the rd experiments for molecules having residual dipolar coupling significantly reduces artifacts. In the method the 15N/13C π pulse phase in the U-element is chosen between x and y. We show that the correctly adjusted sequence is tolerant to miscalibration of the CPMG π pulse power as large as ±10% for most amide 15N and aromatic 13C resonances of proteins.

Analysis of Internal Motions of RNase T1 Complexed with a Productive Substrate Involving 15N NMR Relaxation Measurements

2006 ◽  
Vol 140 (1) ◽  
pp. 43-48
Author(s):  
Yuichiro Yoshida ◽  
Masakazu Tanaka ◽  
Takatoshi Ohkuri ◽  
Yoshitsugu Tanaka ◽  
Taiji Imoto ◽  
...  
Keyword(s):  
Nmr Relaxation ◽  
15N Nmr ◽  
Internal Motions ◽  
15N Nmr Relaxation ◽  
Relaxation Measurements

13C-NMR Relaxation in Three DNA Oligonucleotide Duplexes: Model-Free Analysis of Internal and Overall Motion

Biochemistry ◽  
1994 ◽  
Vol 33 (9) ◽  
pp. 2441-2450 ◽  
Author(s):  
Philip N. Borer ◽  
Steven R. LaPlante ◽  
Anil Kumar ◽  
Nilo Zanatta ◽  
Amy Martin ◽  
...  
Keyword(s):  
13C Nmr ◽  
Nmr Relaxation ◽  
Model Free

scholarly journals Collagen I weakly interacts with the β-sheets of β2-microglobulin and enhances conformational exchange to induce amyloid formation

2019 ◽  
Author(s):  
Cody L. Hoop ◽  
Jie Zhu ◽  
Shibani Bhattacharya ◽  
Caitlyn A. Tobita ◽  
Sheena E. Radford ◽  
...  
Keyword(s):  
Protein Function ◽  
Weak Interactions ◽  
Nmr Relaxation ◽  
Conformational Exchange ◽  
Collagen I ◽  
Solution Nmr ◽  
Amyloid Formation ◽  
Relaxation Methods ◽  
A Minor

ABSTRACTAmyloidogenesis is significant in both protein function and pathology. Amyloid formation of folded, globular proteins is commonly initiated by partial unfolding. However, how this unfolding event is triggered for proteins that are otherwise stable in their native environments is not well understood. The accumulation of the immunoglobulin protein β2-microglobulin (β2m) into amyloid plaques in the joints of long-term hemodialysis patients is the hallmark of Dialysis Related Amyloidosis (DRA). While β2m does not form amyloid unassisted near neutral pH in vitro, the localization of β2m deposits to joint spaces suggests a role for the local extracellular matrix (ECM) proteins, specifically collagens, in promoting amyloid formation. Indeed, collagen and other ECM components have been observed to facilitate β2m amyloid formation, but the large size and anisotropy of the complex, combined with the low affinity of these interactions, has limited atomic-level elucidation of the amyloid-promoting mechanism by these molecules. Using solution NMR approaches that uniquely probe weak interactions and large complexes, we are able to derive binding interfaces for collagen I on β2m and detect collagen I-induced µs–ms timescale dynamics in the β2m backbone. By combining solution NMR relaxation methods and 15N-dark state exchange saturation transfer experiments, we propose a model in which weak, multimodal collagen I–β2m interactions promote exchange with a minor population of an amyloid-competent species to induce fibrillogenesis. The results portray the intimate role of the environment in switching an innocuous protein into an amyloid-competent state, rationalizing the localization of amyloid deposits in DRA.

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