初期段階のSec誘導タンパク質転位の直接シミュレーション
1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.
Journal of the American Chemical Society
|August 3, 2012
まとめ
直接的なシミュレーションは,Sec-transloconチャネルを使用してタンパク質が膜をどのように横断するかを明らかにします. 分子ダイナミクスはシグナルペプチドのドッキングと構成の変化を示し,統合膜タンパク質トポロジーを説明します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- コンピュータ生物学 コンピュータ生物学
背景:
- タンパク質の転位と膜統合は,細胞の基本的なプロセスである.
- Sec-transloconチャネルは,タンパク質が膜を横断することを促進します.
- 統合膜タンパク質トポロジーのメカニズムを理解することは極めて重要です.
研究 の 目的:
- 初期段階のタンパク質転位と膜統合のメカニズム的特徴を解明する.
- タンパク質分泌と膜挿入の調節における分子相互作用の役割を調査する.
- タンパク質トポロジーの実験的に観察された相関関係を理解するための計算的基礎を提供すること.
主な方法:
- 非均衡タンパク質の成長とマイクロ秒分子の分子動態シミュレーションを組み合わせた新しい計算プロトコルを利用しました.
- Sec-translocon.conにタンパク質を挿入する複数の長期スケールシミュレーションを分析しました.
- トランスロコンの側面ゲートと脂質二重層との分子相互作用を調査した.
主要な成果:
- トランスロコン側ゲート (LG) に同定された信号ペプチドック.
- タンパク質の挿入中に,トランスロコンのLGヘリクスの大規模な形状的再配置が観察されました.
- 塩橋と水害性コンタクトが新生タンパク質構成と統合膜タンパク質トポロジーにどのように影響するかを示した (タイプII vs. タイプIII) である.
結論:
- 直接的なシミュレーションは,タンパク質の転位と膜統合に関する重要な力学的洞察を提供します.
- 新生タンパク質,トランスロコン,および脂質を含む特定の分子相互作用は,タンパク質トポロジーの重要な調節因子である.
- この発見は,タンパク質のトポロジーとトランスロコンの機能に関する実験データを解釈するためのメカニズム的基礎を提供します.
関連する概念動画
Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
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...
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...
Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Protein Dynamics in Living Cells
Different fluorescence-based techniques are used to study the protein dynamics in living cells. These techniques include FRAP, FRET, and PET.
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...


