Intrinsically Disordered Region Modulates Ligand Binding in Glutaredoxin 1 from Trypanosoma Brucei

2021 ◽  
Author(s):  
Galo. E. Balatti ◽  
G. Patricio Barletta ◽  
Gustavo Parisi ◽  
Silvio. C. E. Tosatto ◽  
Massimo Bellanda ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Trypanosoma Brucei ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region

Association/dissociation Mechanisms of Intrinsically Disordered Region of Protein Beyond Conformational Selection and Induced Fit

2019 ◽  
Author(s):  
Duy Phuoc Tran ◽  
Akio Kitao
Keyword(s):  
Free Energy ◽  
Transcriptional Activation ◽  
Binding Free Energy ◽  
Energy Structure ◽  
Induced Fit ◽  
Hydrogen Bond Formation ◽  
Conformational Selection ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region ◽  
Dissociation Mechanisms

<p>We investigate association and dissociation mechanisms of a typical intrinsically disordered region (IDR), transcriptional activation subdomain of tumor repressor protein p53 (TAD-p53) with murine double-minute clone 2 protein (MDM2). Using the combination of cycles of association and dissociation parallel cascade molecular dynamics, multiple standard MD, and Markov state model, we are successful in obtaining the lowest free energy structure of MDM2/TAD-p53 complex as the structure very close to that in crystal without prior knowledge. This method also reproduces the experimentally measured standard binding free energy, and association and dissociation rate constants solely with the accumulated MD simulation cost of 11.675 μs, in spite of the fact that actual dissociation occurs in the order of a second. Although there exist a few complex intermediates with similar free energies, TAD-p53 first binds MDM2 as the second lowest free energy intermediate dominantly (> 90% in flux), taking a form similar to one of the intermediate structures in its monomeric state. The mechanism of this step has a feature of conformational selection. In the second step, dehydration of the interface, formation of π-π stackings of the side-chains, and main-chain relaxation/hydrogen bond formation to complete α-helix take place, showing features of induced fit. In addition, dehydration (dewetting) is a key process for the final relaxation around the complex interface. These results demonstrate a more fine-grained view of the IDR association/dissociation beyond classical views of protein conformational change upon binding.</p>

scholarly journals Conformational Ensemble and Biological Role of the TCTP Intrinsically Disordered Region: Influence of Calcium and Phosphorylation

2018 ◽  
Vol 430 (11) ◽  
pp. 1621-1639 ◽  
Author(s):  
Florian Malard ◽  
Nadine Assrir ◽  
Mouad Alami ◽  
Samir Messaoudi ◽  
Ewen Lescop ◽  
...  
Keyword(s):  
Biological Role ◽  
Conformational Ensemble ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region

Synaptotagmin I’s Intrinsically Disordered Region Interacts with Synaptic Vesicle Lipids and Exerts Allosteric Control over C2A

Biochemistry ◽  
2016 ◽  
Vol 55 (21) ◽  
pp. 2914-2926 ◽  
Author(s):  
Michael E. Fealey ◽  
Ryan Mahling ◽  
Anne M. Rice ◽  
Katie Dunleavy ◽  
Stephanie E. G. Kobany ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Allosteric Control ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region

scholarly journals Multiple Interactions of the Intrinsically Disordered Region between the Helicase and Nuclease Domains of the Archaeal Hef Protein

2014 ◽  
Vol 289 (31) ◽  
pp. 21627-21639 ◽  
Author(s):  
Sonoko Ishino ◽  
Takeshi Yamagami ◽  
Makoto Kitamura ◽  
Noriyuki Kodera ◽  
Tetsuya Mori ◽  
...  
Keyword(s):  
Intrinsically Disordered ◽  
Intrinsically Disordered Region ◽  
Multiple Interactions
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