Role of Electrostatic Interactions in Transient Encounter Complexes in Protein−Protein Association Investigated by Paramagnetic Relaxation Enhancement

2007 ◽  
Vol 129 (43) ◽  
pp. 12954-12955 ◽  
Author(s):  
Jeong-Yong Suh ◽  
Chun Tang ◽  
G. Marius Clore
Keyword(s):  
Electrostatic Interactions ◽  
Paramagnetic Relaxation ◽  
Paramagnetic Relaxation Enhancement ◽  
Protein Association

scholarly journals Atomic view of cosolute-induced protein denaturation probed by NMR solvent paramagnetic relaxation enhancement

2021 ◽  
Vol 118 (34) ◽  
pp. e2112021118
Author(s):  
Yusuke Okuno ◽  
Janghyun Yoo ◽  
Charles D. Schwieters ◽  
Robert B. Best ◽  
Hoi Sung Chung ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Electrostatic Interactions ◽  
Dynamic Equilibrium ◽  
Protein Denaturation ◽  
Group Versus ◽  
Paramagnetic Relaxation ◽  
Paramagnetic Relaxation Enhancement ◽  
Native State ◽  
Unfolded State ◽  
Loop Regions

The cosolvent effect arises from the interaction of cosolute molecules with a protein and alters the equilibrium between native and unfolded states. Denaturants shift the equilibrium toward the latter, while osmolytes stabilize the former. The molecular mechanism whereby cosolutes perturb protein stability is still the subject of considerable debate. Probing the molecular details of the cosolvent effect is experimentally challenging as the interactions are very weak and transient, rendering them invisible to most conventional biophysical techniques. Here, we probe cosolute–protein interactions by means of NMR solvent paramagnetic relaxation enhancement together with a formalism we recently developed to quantitatively describe, at atomic resolution, the energetics and dynamics of cosolute–protein interactions in terms of a concentration normalized equilibrium average of the interspin distance, 〈r−6〉norm, and an effective correlation time, τc. The system studied is the metastable drkN SH3 domain, which exists in dynamic equilibrium between native and unfolded states, thereby permitting us to probe the interactions of cosolutes with both states simultaneously under the same conditions. Two paramagnetic cosolute denaturants were investigated, one neutral and the other negatively charged, differing in the presence of a carboxyamide group versus a carboxylate. Our results demonstrate that attractive cosolute–protein backbone interactions occur largely in the unfolded state and some loop regions in the native state, electrostatic interactions reduce the 〈r−6〉norm values, and temperature predominantly impacts interactions with the unfolded state. Thus, destabilization of the native state in this instance arises predominantly as a consequence of interactions of the cosolutes with the unfolded state.

scholarly journals Structure-Free Validation of Residual Dipolar Coupling and Paramagnetic Relaxation Enhancement Measurements of Disordered Proteins

Biochemistry ◽  
2015 ◽  
Vol 54 (46) ◽  
pp. 6876-6886 ◽  
Author(s):  
Francisco N. Newby ◽  
Alfonso De Simone ◽  
Maho Yagi-Utsumi ◽  
Xavier Salvatella ◽  
Christopher M. Dobson ◽  
...  
Keyword(s):  
Dipolar Coupling ◽  
Residual Dipolar Coupling ◽  
Paramagnetic Relaxation ◽  
Paramagnetic Relaxation Enhancement ◽  
Disordered Proteins
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