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Updated: May 30, 2026

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Measuring Peptide Translocation into Large Unilamellar Vesicles
Published on: January 27, 2012
均衡状態下での水害性ペプチドのインシリコ分割とトランスメブラン挿入
Jakob P Ulmschneider1, Jeremy C Smith, Stephen H White
1IWR University of Heidelberg, Germany. jakob@ulmschneider.com
Journal of the American Chemical Society
|August 25, 2011
まとめ
分子ダイナミクスシミュレーションにより,ヒドロホビックペプチドが脂質二重層にどのように挿入されるかが明らかになりました. この研究は,トランスメブランタンパク質の挿入のための物理的および生物学的な水害性スケールとの関係を明らかにします.
科学分野:
- バイオフィジックス 生物物理学
- 分子生物学は分子生物学である.
- コンピューティング・ケミストリー
背景:
- 新生型トランスメブラン (TM) ポリペプチドは,トランスロコン機構を通じて脂質二重層に挿入されます.
- 生物学的水性スケールは物理的なスケールと相関しているが,実験的な溶解性の制限のために正確な関係は不明である.
研究 の 目的:
- 水性ペプチドを脂質二重層に挿入する自由エネルギーを直接測定する.
- ペプチド挿入の分割経路と運動学を調査する.
- シミュレーションで得られた自由エネルギーの分割を,トランスロコンの実験データと比較する.
主な方法:
- ポリユキンのセグメントが脂質二重層の内外に分裂するマイクロ秒分子動力学 (MD) シミュレーション.
- 均衡状態からの自由挿入エネルギーを直接決定する (表面限定対外膜内挿入).
主要な成果:
- 水性ペプチドは,表面に結合した状態または膜に挿入された状態に分裂する;水溶性状態は観察されなかった.
- 自由エネルギーの移転は温度に依存しないことが判明し,表面からバイラーへの挿入のためのゼロエントロピープロセスを示唆しています.
- シミュレートされた自由エネルギー分割は,トランスロコン実験値と相関しているが,短いペプチドを好むシフトを示した.
結論:
- MDシミュレーションは,ペプチド膜分割の自由エネルギーを決定する直接的な方法を提供し,実験的な溶解性の問題を克服します.
- トランスロコン媒介による分割は,自発的な表面対壁層分割に関連していますが,それと同等ではありません.
- 自由エネルギー移転の温度独立は,ペプチド挿入熱力学を理解する上で重要な意味を持つ.
関連する概念動画
Translocation of Proteins into the Mitochondria
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Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Insertion of Multi-pass Transmembrane Proteins in the RER
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The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Insertion of Single-pass Transmembrane Proteins in the RER
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Single-pass Transmembrane Proteins
Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...
Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...

