The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C
Abstract
:1. Introduction
2. Results
2.1. Selection of hCC Variants—What Are the Differences between hCC Variants’ Properties?
2.2. Size Exclusion Chromatography—How Does the hCC Monomer-Dimer Equilibrium Change in a Micellar Environment?
2.3. Circular Dichroism—Does a Micellar Environment Influence the Secondary Structure of hCC?
2.4. Nuclear Magnetic Resonance—Which Fragments in the hCC Structure Bind to the Micelle?
2.5. Molecular Dynamics—What Kind of Global and Local Structural Changes in the hCC Structure May Occur in a Virtual Micelle Environment?
2.5.1. DPC:SDS Mixed Micelle—hCC Monomer (WT and hCC V57G)
2.5.2. DPC:SDS Mixed Micelle—hCC Dimer (WT and V57P)
2.5.3. Molecular Dynamics—Fluctuations
3. Discussion
3.1. Size Exclusion Chromatography—The DPC:SDS Micelle Reverses the hCC Dimerization Process
3.2. Circular Dichroism—The Micelle Influences the Level of Order of the hCC Secondary Structure
3.3. Nuclear Magnetic Resonance—Micelle Binds to the Flexible Parts of hCC Structure
3.4. Molecular Dynamics—Micelle Causes Structural Displacement in the Flexible Parts of hCC Structure
4. Conclusions
5. Materials and Methods
5.1. Expression and Purification of Labeled and Unlabeled Proteins
5.2. hCC WT Dimerization
5.3. Micelle Sample Preparation
5.4. Analytical Size Exclusion Chromatography of hCC
5.5. Circular Dichroism Spectroscopy
5.6. NMR Spectroscopy
5.7. Molecular Dynamics
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CD | Circular dichroism |
hCC | human cystatine C |
hCC V57G | Val57→Gly mutant of human cystatine C |
hCC V57P | Val57→Pro mutant of human cystatine C |
DMPC | dimyristoylphosphocholine |
DPC | dodecylphosphocholine |
SDS | sodium dodecyl sulfate |
CMC | critical micelle concentration |
SEC | size exclusion chromatography |
RMSD | root mean square distance |
SASA | solvent accessible surface area |
DSS | sodium 2,2-dimethyl-2-silapentane-5-sulfonat |
WT | wild-type |
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Structure | Whole hCC | Protein (Monomer or Dimer) 1 | Protein (Monomer) 2 |
---|---|---|---|
hCC-1 | 6.27 ± 2.71 Å | 2.05 ± 0.89 Å | 1.38 ± 0.60 Å |
hCC-2 | 2.85 ± 1.23 Å | 2.72 ± 1.18 Å | 2.49 ± 1.07 Å |
hCC-3 | 4.57 ± 1.98 Å | 2.74 ± 1.18 Å | 1.73 ± 0.75 Å |
V57G-1 | 4.00 ± 1.73 Å | 2.56 ± 1.10 Å | 1.48 ± 0.64 Å |
V57G-2 | 3.64 ± 1.58 Å | 1.84 ± 0.80 Å | 1.56 ± 0.68 Å |
V57G-3 | 2.52 ± 1.09 Å | 2.48 ± 1.07 Å | 1.53 ± 0.66 Å |
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Jurczak, P.; Sikorska, E.; Czaplewska, P.; Rodziewicz-Motowidlo, S.; Zhukov, I.; Szymanska, A. The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C. Membranes 2021, 11, 17. https://doi.org/10.3390/membranes11010017
Jurczak P, Sikorska E, Czaplewska P, Rodziewicz-Motowidlo S, Zhukov I, Szymanska A. The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C. Membranes. 2021; 11(1):17. https://doi.org/10.3390/membranes11010017
Chicago/Turabian StyleJurczak, Przemyslaw, Emilia Sikorska, Paulina Czaplewska, Sylwia Rodziewicz-Motowidlo, Igor Zhukov, and Aneta Szymanska. 2021. "The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C" Membranes 11, no. 1: 17. https://doi.org/10.3390/membranes11010017
APA StyleJurczak, P., Sikorska, E., Czaplewska, P., Rodziewicz-Motowidlo, S., Zhukov, I., & Szymanska, A. (2021). The Influence of the Mixed DPC:SDS Micelle on the Structure and Oligomerization Process of the Human Cystatin C. Membranes, 11(1), 17. https://doi.org/10.3390/membranes11010017