The 2β Splice Variation Alters the Structure and Function of the Stromal Interaction Molecule Coiled-Coil Domains
Abstract
:1. Introduction
2. Results
2.1. The 2β Insertion Decreases the α-Helicity of OASF
2.2. The 2β Insert Reduces the Thermal Stability of STIM1-OASF
2.3. The 2β Insert Exacerbates Ca2+-Induced Hydrophobic Exposure of OASF
2.4. Ca2+ Minimally Affects the α-Helicity of the OASF Domains with or without 2β
2.5. Ca2+ Thermally Destabilizes STIM1-OASF and STIM1-2β-OASF
2.6. Ca2+ Increases the Aggregation Propensity of OASF
2.7. The 2β Insertion Does Not Alter OASF Dimer Quaternary Structure
2.8. The 2β Insertion Causes Local Changes in OASF Structure
2.9. The 2β Insertion Inhibits OASF Function Independent of the STIM2 Context
3. Discussion
4. Methods
4.1. STIM OASF Expression and Purification
4.2. Far UV CD Spectroscopy
4.3. ANS Fluorescence Spectroscopy
4.4. SEC-MALS
4.5. DLS
4.6. SAXS
4.7. Fura-2 Fluorimetry
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Protein | Ca2+ (a) | Elution Volume (mL) (b) | Molecular Weight (kDa) (c) | Stoichiometric Ratio (d) |
---|---|---|---|---|
STIM1-OASF | − | 13.59 ± 0.14 | 67.6 ± 1.4 | 2.18 |
STIM1-2β-OASF | − | 12.69 ± 0.05 | 64.9 ± 1.7 | 2.02 |
STIM2-OASF | − | 12.69 ± 0.02 | 61.4 ± 1.3 | 1.98 |
STIM2-2β-OASF | − | 12.85 ± 0.02 | 60.8 ± 0.2 | 1.96 |
STIM1-OASF | + | 13.55 ± 0.01 | 62.3 ± 3.7 | 2.00 |
STIM1-2β-OASF | + | 13.03 ± 0.30 | 63.0 ± 1.3 | 1.96 |
STIM2-OASF | + | 12.76 ± 0.08 | 61.8 ± 2.1 | 1.99 |
STIM2-2β-OASF | + | 12.87 ± 0.20 | 61.3 ± 1.6 | 1.97 |
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Chung, S.; Zhang, M.; Stathopulos, P.B. The 2β Splice Variation Alters the Structure and Function of the Stromal Interaction Molecule Coiled-Coil Domains. Int. J. Mol. Sci. 2018, 19, 3316. https://doi.org/10.3390/ijms19113316
Chung S, Zhang M, Stathopulos PB. The 2β Splice Variation Alters the Structure and Function of the Stromal Interaction Molecule Coiled-Coil Domains. International Journal of Molecular Sciences. 2018; 19(11):3316. https://doi.org/10.3390/ijms19113316
Chicago/Turabian StyleChung, Steve, MengQi Zhang, and Peter B. Stathopulos. 2018. "The 2β Splice Variation Alters the Structure and Function of the Stromal Interaction Molecule Coiled-Coil Domains" International Journal of Molecular Sciences 19, no. 11: 3316. https://doi.org/10.3390/ijms19113316