Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility
Abstract
:1. Introduction
2. Results and Discussion
2.1. V66M Polymorphism Influences the Conformation of hproBDNF in Solution
2.2. V66M Polymorphism Affects the Thermostability and the Conformational Plasticity of hproBDNF in Solution
3. Conclusions
4. Materials and Methods
4.1. Fourier Transform Infrared Spectroscopy (FT-IR)
4.2. Limited Proteolysis
4.3. Differential Scanning Fluorimetry (DSF)
4.4. Small-Angle X-ray Scattering Data Collection and Processing
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Data Collection Parameters | hproBDNF V66M | hproBDNF |
---|---|---|
Instrument | P12 (PETRA III) | P12 (PETRA III) |
Beam geometry (mm2) | 0.2 × 0.12 | 0.2 × 0.12 |
Wavelength (Å) | 1.24 | 1.24 |
s range (Å−1) | 0.003–0.445 | 0.003–0.445 |
Concentration range (mg/mL) | 0.14–1.45 | 0.10–1.48 |
Temperature (K) | 283 | 283 |
Structural parameters | ||
I(0) (A.U.) [from p(r)] | 0.02100 ± 0.0002 | 0.0177 ± 0.0002 |
Rg (Å) [from p(r)] | 35.5 ± 0.05 | 37.2 ± 0.06 |
I(0) (A.U.) [from Guinier] | 0.02263 ± 0.0002 | 0.0182 ± 0.0002 |
Rg (Å) [from Guinier] | 35.5 ± 0.05 | 37.1 ± 0.06 |
Dmax (Å) | 115 ± 5 | 125 ± 6 |
Vp Porod volume estimate (Å3) | 85,675 ± 6000 | 86,750 ± 6000 |
Molecular mass determination (Da) | ||
MM [from I(0)] | 55,440 ± 6000 | 48,048 ± 6000 |
MM [from Porod volume] | 50,400 ± 6000 | 51,030 ± 6000 |
Calculated monomeric MM from sequence | 25,930 | 25,930 |
Software employed | ||
Primary data reduction | PRIMUS | PRIMUS |
Data processing | GNOM | GNOM |
Rigid body modeling | CORAL/EOM | CORAL/EOM |
Validation and averaging | DAMAVER | DAMAVER |
Three-dimensional graphic representations | PYMOL | PYMOL |
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Covaceuszach, S.; Peche, L.Y.; Konarev, P.V.; Grdadolnik, J.; Cattaneo, A.; Lamba, D. Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility. Int. J. Mol. Sci. 2022, 23, 6596. https://doi.org/10.3390/ijms23126596
Covaceuszach S, Peche LY, Konarev PV, Grdadolnik J, Cattaneo A, Lamba D. Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility. International Journal of Molecular Sciences. 2022; 23(12):6596. https://doi.org/10.3390/ijms23126596
Chicago/Turabian StyleCovaceuszach, Sonia, Leticia Yamila Peche, Petr Valeryevich Konarev, Joze Grdadolnik, Antonino Cattaneo, and Doriano Lamba. 2022. "Untangling the Conformational Plasticity of V66M Human proBDNF Polymorphism as a Modifier of Psychiatric Disorder Susceptibility" International Journal of Molecular Sciences 23, no. 12: 6596. https://doi.org/10.3390/ijms23126596