直接模拟早期阶段的Sec辅助蛋白质转位
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
概括
直接模拟揭示了蛋白质如何使用Sec-translocon通道穿越膜. 分子动力学显示信号对接和构造变化,解释了整体膜蛋白质拓.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- 蛋白质转位和膜融合是细胞的基本过程.
- 这种Sec-translocon通道有助于蛋白质通过膜.
- 了解积分膜蛋白拓学的机制至关重要.
研究的目的:
- 阐明早期蛋白质转位和膜融合的机制特征.
- 研究分子相互作用在调节蛋白质分泌和膜插入中的作用.
- 为理解蛋白质拓学中实验观察到的相关性提供计算基础.
主要方法:
- 利用了一种新的计算协议,将非平衡蛋白质生长与微秒分子动力学模拟相结合.
- 对Sec-translocon.con中蛋白质插入的多个长时间模拟进行了分析.
- 研究了跨环子侧门和脂质双层的分子相互作用.
主要成果:
- 识别的信号在转位侧门 (LG) 进行对接.
- 在蛋白质插入过程中观察到转位LG螺旋体的大规模形状重排.
- 证明了盐桥和疏水接触如何影响新生的蛋白质构造和整体膜蛋白质拓 (II型与II型对比). 第三种类型).
结论:
- 直接模拟提供了对蛋白质转位和膜集成的关键机理见解.
- 涉及新生的蛋白质,转基因和脂质的特定分子相互作用是蛋白质拓学的关键调节者.
- 这些发现为解释有关蛋白质拓和转位子功能的实验数据提供了机制基础.
相关概念视频
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...


