ハンティングチンエクソン-1 N-ターミナスの構造とダイナミクス:溶液NMR展望
Maria Baias1, Pieter E S Smith1, Koning Shen2
1Department of Chemical Physics, Weizmann Institute of Science , Rehovot 76100, Israel.
Journal of the American Chemical Society
|January 14, 2017
まとめ
研究者はNMRと計算を用いてハンティングチンタンパク質 (Htt) エクソン1の構造を研究した. pHがHttに影響する
科学分野:
- 神経科学
- 生物化学
- 構造生物学
背景:
- ハンチントン病のような 神経退行性疾患は タンパク質の誤折りや 結合を伴うものです
- ハンチントンタンパク質 (Htt) エクソン1は,ポリグルタミン (polyQ) 経路で,ハンチントン病の病理学の中心です.
- 溶解性Htt形状を理解することは,毒性を引き起こす可能性があるため,極めて重要です.
研究 の 目的:
- Htt エクソン1の溶液構造を解明する.
- Httの集積と毒性における N17ドメインの役割を調査する.
- 溶解性から集積性Htt形状への移行を理解する.
主な方法:
- 核磁気共振 (NMR) スペクトロスコーピーは,計算によるアプローチと組み合わせられています.
- 最小限のHttエクソン1構造 (N17,ポリQ経路,ポリプロリン領域) を利用した.
- pH定位と多次元NMRを用いて,スペクトルの割り当てと構造の解明を行いました.
主要な成果:
- N17ドメインとpolyQ経路の完全なNMR割り当てを達成しました.
- 低pHは,ポリQ経路に広がる螺旋状のN17領域を持つ溶解性Htt構造を安定させる.
- ニュートラルなpHは,主に構造化されていないN17とpolyQ領域をもたらす.
結論:
- N17ドメインの構造とポリQ経路との相互作用はpHに依存する.
- 異なるpHレベルでのHttエクソン1の構造の変化は,集積の調節メカニズムを示唆する.
- この研究は,ハンティントン病に関連した HTT 構造のダイナミクスに関する 分子洞察を提供します.
関連する概念動画
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
1.8K
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
1.8K
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
1.4K
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
1.4K
01:192D NMR: Heteronuclear Single-Quantum Correlation Spectroscopy (HSQC)
1.5K
Heteronuclear single-quantum correlation spectroscopy (HSQC) is a 2D NMR technique that reveals one-bond correlations between hydrogen and a heteronucleus. The HSQC experiment is similar to the heteronuclear correlation experiment (HETCOR) but is more sensitive. In the HSQC spectrum, the proton chemical shift is plotted on the horizontal F2 axis, while the 13C chemical shift is plotted on the vertical F1 axis. The corresponding proton and 13C spectra are also shown. The HSQC contour plot does...
1.5K
00:48¹H NMR of Labile Protons: Deuterium (²H) Substitution
1.5K
This lesson illustrates the role of deuterium substitution in simplifying the NMR spectrum of compounds comprising labile protons. One method employed is the use of deuterium. Amongst the three isotopes of hydrogen, deuterium (2H) has a nucleus composed of one proton and one neutron. When the D2O solvent is added to a pure dry ethanol solution, its labile proton is substituted with deuterium.
1.5K
01:182D NMR: Overview of Heteronuclear Correlation Techniques
849
Heteronuclear correlation spectroscopy is an analytical technique that investigates the coupling between different types of nuclei, often a proton and an X-nucleus, such as carbon-13 or nitrogen-15. This method is commonly used in nuclear magnetic resonance (NMR) spectroscopy to gain insights into complex chemical compounds' structural and compositional aspects. A typical heteronuclear correlation spectrum displays X-nucleus chemical shifts on one axis and a proton spectrum on the other...
849