Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations
Abstract
:1. Introduction
2. Results
2.1. δC1b-Phorbol and δC1b-Bryostatin Show Differential Lipid Headgroup Engagement
2.2. δC1b-Phorbol Interacts with Cholesterol in Heterogenous Membranes
2.3. δC1b-Merle27 Mimics δC1b-Phorbol in Insertion Depth and Cholesterol Interactions
3. Discussion
4. Materials and Methods
4.1. Preparation of Protein–Ligand Complexes
4.1.1. δC1b-Phorbol Complex
4.1.2. δC1b-Bryostatin and δC1b-Merle 27 Complexes
4.2. Molecular Dynamics Simulations
4.3. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Lipid | Upper Leaflet | Lower Leaflet |
---|---|---|
Cholesterol | 14 (21%) | 13 (22%) |
POPC | 13 (20%) | 12 (20%) |
POPE | 18 (27%) | 17 (29%) |
SOPS | 8 (12%) | 7 (12%) |
POPA | 2 (3%) | 1 (2%) |
PLPIP35 | 4 (6%) | 3 (5%) |
CER160 | 7 (11%) | 6 (10%) |
Total | 66 | 59 |
Lipid | Upper Leaflet | Lower Leaflet |
---|---|---|
Cholesterol | 16 (22%) | 16 (24%) |
POPC | 15 (20%) | 13 (19%) |
POPE | 19 (26%) | 18 (27%) |
SOPS | 8 (11%) | 8 (12%) |
POPA | 3 (4%) | 2 (3%) |
PLPIP35 | 5 (7%) | 4 (6%) |
CER160 | 7 (10%) | 6 (9%) |
Total | 73 | 67 |
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Judge, P.T.; Overall, S.A.; Barnes, A.B. Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations. Int. J. Mol. Sci. 2023, 24, 4598. https://doi.org/10.3390/ijms24054598
Judge PT, Overall SA, Barnes AB. Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations. International Journal of Molecular Sciences. 2023; 24(5):4598. https://doi.org/10.3390/ijms24054598
Chicago/Turabian StyleJudge, Patrick T., Sarah A. Overall, and Alexander B. Barnes. 2023. "Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations" International Journal of Molecular Sciences 24, no. 5: 4598. https://doi.org/10.3390/ijms24054598