A Thermodynamic Model of Auto‐regulated Protein Assembly by a Supramolecular Scaffold

Rennie, Martin L.; Crowley, Peter B.

doi:10.1002/cphc.201900153

“…Previously, using NMR spectroscopy and isothermal titration calorimetry, we characterized in detail the auto-regulated assembly of cytc by sclx8. 29,31 In brief, the HSQC spectrum of cytc is broadened beyond detection at ~1 eq. sclx8 due to tetramer formation.…”

Section: Resultsmentioning

confidence: 99%

“…22,29,30 We have demonstrated controlled assembly of cationic proteins by anionic macrocycles such as sulfonato-calix[n]arene (sclxn). 22,[29][30][31] Our focus is on the lysine-rich cytochrome c (cytc), a redox active building block that is applied widely in biosensor development. 32,33 Previously, we reported auto-regulated assembly of cytc by sclx8.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tuning Protein Frameworks via Auxiliary Supramolecular Interactions

Engilberge

¹

,

Rennie

²

,

Dumont

³

et al. 2019

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Protein crystals with their precise, periodic array of functional building blocks have potential applications in biomaterials, sensing and catalysis. This paper describes how a highly-porous crystalline framework of a cationic redox protein and an anionic macrocycle can be modulated by a small cationic effector. Ternary composites of protein (~13 kDa), calix[8]arene (~1.5 kDa) and effector (~0.2 kDa) formed distinct crystalline architectures, dependent on the effector concentration and the crystallization technique. A combination of X-ray crystallography and DFT calculations was used to decipher the framework variations, which appear to depend on a calixarene conformation change mediated by the effector. This "switch" calixarene was observed in three states, each of which is associated with a different interaction network. Two structures obtained by co-crystallization with the effector contained an additional protein "pillar", resulting in framework duplication and decreased porosity. These results suggest how protein assembly can be engineered by supramolecular host-guest interactions.

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“…Classical all-atom molecular dynamics (MD) simulations have been performed using the Amber package 41 and the Ambertools suite. A single Cytc protein structure was used (108 residues), taken from the H3 form of the sclx 8 -Cytc complex (Saccharomyces cerevisae cytochrome c C102T, PDB ID 6GD6 10,25 ). The heme group 42 was connected to the H18 and M80 residues through the use of "Metal Center Parameter Builder" (MCPB) Ambertool 43 .…”

Section: Force Field Parameters and MD Simulationsmentioning

confidence: 99%

Molecular dynamics approach for capturing calixarenes--proteins interactions: the case of cytochrome c

Bartocci¹,

szczepaniak²,

Jiang³

et al. 2020

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Here, we propose a molecular dynamics investigation of the supramolecular association of sulfonatedcalix-[8]-arenes to cytochrome c. The binding sites prone to interactions with sulfonated calixarenescan be identified without prior knowledge of the X-ray structure, and the binding free energiesestimated by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) post-analysis arefound to be in neat agreement with the isothermal titration calorimetry (ITC) measurements The per-residuedecomposition reveals the detailed picture of this electrostatically-driven association and notably therole of the arginine R13 as a bridge residue between the two main anchoring sites. In addition,the analysis of the residue behavior by means of a supervised machine learning protocol unveils the formation of an hydrogen bond network far from the binding sites, increasing the rigidity of theprotein.

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“…Regulated protein assembly and disassembly is fundamental in biology 1 . These mechanisms, as many biophysical and biochemical processes [2][3][4][5] , lead to supramolecular aggregates and macromolecules.…”

Section: Introductionmentioning

confidence: 99%

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

Bartocci¹,

Szczepaniak²,

Jiang³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Here, we propose a molecular dynamics investigation of the supramolecular association of sulfonatedcalix-[8]-arenes to cytochrome c. The binding sites prone to interactions with sulfonated calixarenescan be identified without prior knowledge of the X-ray structure, and the binding free energiesestimated by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) post-analysis arefound to be in neat agreement with the isothermal titration calorimetry (ITC) measurements The per-residuedecomposition reveals the detailed picture of this electrostatically-driven association and notably therole of the arginine R13 as a bridge residue between the two main anchoring sites. In addition,the analysis of the residue behavior by means of a supervised machine learning protocol unveils the formation of an hydrogen bond network far from the binding sites, increasing the rigidity of theprotein.

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A Thermodynamic Model of Auto‐regulated Protein Assembly by a Supramolecular Scaffold

Cited by 10 publications

References 48 publications

Tuning Protein Frameworks via Auxiliary Supramolecular Interactions

Tuning Protein Frameworks via Auxiliary Supramolecular Interactions

Molecular dynamics approach for capturing calixarenes--proteins interactions: the case of cytochrome c

Capturing the Supramolecular Association of Calixarenes onto Proteins Relying on Molecular Dynamics Simulations: The Case of Cytochrome C

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