Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain
Abstract
1. Introduction
2. Methods
2.1. System Preparation and Conformational Sampling
2.2. Anharmonic Conformational Analysis (ANCA)
2.3. Temporal Decorrelation of Fourth-Order on Time-Delayed Cumulant Matrices
2.4. Identifying Conformational Sub-States
2.5. Experimental Methods
3. Results
3.1. Partial Unfolding of M11- Facilitates Opening/Closing of BH3D Binding Site
3.2. Structural Intermediates of the Apo- to Holo-M11 Show Transient Unfolding of 2
3.3. Perturbing Hydrophobic Interactions Farther from M11 Binding Cleft Impact BECN1 BH3D Binding
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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(M) | () | H (kJ/mol) | G (kJ/mol) | S (J/K·mol) | Distance (Å) | |
---|---|---|---|---|---|---|
WT | - | |||||
F48A | 9.4 | |||||
A63K | 11.9 | |||||
Y56A | 9.7 | |||||
F17A | N/A | N/A | N/A | N/A | N/A | 19.7 |
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Ramanathan, A.; Parvatikar, A.; Chennubhotla, S.C.; Mei, Y.; Sinha, S.C. Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain. Biomolecules 2020, 10, 1308. https://doi.org/10.3390/biom10091308
Ramanathan A, Parvatikar A, Chennubhotla SC, Mei Y, Sinha SC. Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain. Biomolecules. 2020; 10(9):1308. https://doi.org/10.3390/biom10091308
Chicago/Turabian StyleRamanathan, Arvind, Akash Parvatikar, Srinivas C. Chennubhotla, Yang Mei, and Sangita C. Sinha. 2020. "Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain" Biomolecules 10, no. 9: 1308. https://doi.org/10.3390/biom10091308
APA StyleRamanathan, A., Parvatikar, A., Chennubhotla, S. C., Mei, Y., & Sinha, S. C. (2020). Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain. Biomolecules, 10(9), 1308. https://doi.org/10.3390/biom10091308