NMRによって決定されるトランスロカゼモーターSecAによる信号配列認識の構造的基礎
Ioannis Gelis1, Alexandre M J J Bonvin, Dimitra Keramisanou
1Department of Chemistry, Rutgers University, Newark, NJ 07102, USA.
Cell
|November 21, 2007
まとめ
研究者らは,シグナルペプチドがSecA,Secトランスロカゼのモータータンパク質に結合する方法を明らかにした. この結合は,タンパク質の輸出に不可欠であり,SecaAの特定の溝を含み,細胞タンパク質の輸送に関する洞察を明らかにします.
科学分野:
- 分子生物学は分子生物学である.
- タンパク質生化学 タンパク質生化学
- セルラー輸送メカニズム セルラー輸送メカニズム
背景:
- タンパク質の輸出は,受容体によって認識される信号配列に依存して,細胞機能に不可欠です.
- Secトランスロケーション系,特にSecAATPアゼモーターは,タンパク質のトランスロケーションに重要な役割を果たします.
- SecAによるシグナルシーケンスの認識の正確なメカニズムは,ほとんど未定義のままです.
研究 の 目的:
- SecAによる信号ペプチド認識の構造的基礎を決定する.
- タンパク質転位を媒介するSeCA構造の役割を明らかにする.
- そのC端尾とSecBのシャペロンによるSecA活動の調節を調査する.
主な方法:
- NMR光譜を用いた信号ペプチド-SecA複合体の溶液構造の決定.
- 結合相互作用の分析,水嫌性および静電力を含む.
- シグナルペプチド結合が破壊されたときの転位欠陥を評価するための機能分析.
主要な成果:
- シグナルペプチドは,SecAの柔軟な溝に結合するとアルファヘリル構造を採用します.
- SecAは,このグリューブ内の水性および静電性相互作用の両方を通じて,多様な信号配列を認識します.
- SecAへのシグナルペプチド結合の障害は,重要なタンパク質転位欠陥につながる.
- SecAのC端尾は結合を阻害し,SecBのシェパロンによって緩和されるプロセスである.
- SecAは溶液中の2つの異なる形状に存在し,ダイナミックな転位機構を示唆しています.
結論:
- この研究は,タンパク質輸出の重要なステップであるSecAへのシグナルペプチド結合の構造的メカニズムを明らかにしています.
- SecAの柔軟な溝は,さまざまな信号配列の普遍的な認識サイトとして機能します.
- C端末のテールとSecBチャペロンによる規制は,SecAの活動を微調整する.
- SecAの構成動態は,ポリペプチド転位プロセスに関する洞察を提供します.
関連する概念動画
Signal Sequences and Sorting Receptors
Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
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...
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.
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...
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...


