トランスロコン・アセンブリによって引き起こされるディスルファイドの再編成は,リポポリサッカリドの輸出を制御する
Shu-Sin Chng1, Mingyu Xue, Ronald A Garner
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
まとめ
グラム陰性細菌におけるリポポリサッカリド輸送タンパク質D (LptD) の折りたたみには,2つのタンパク質複合体が必要です. LptEタンパク質は,LptDのディスルファイド結合の再編成を誘発する.
科学分野:
- 微生物学 微生物学とは
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- リポポリサッカリド (LPS) は,グラム陰性細菌の外膜の完全性および生存能力にとって不可欠です.
- LptDタンパク質は,バクテリアの外膜にLPSの転位を促進します.
- LptDはLptEと複合体を形成し,LPSトランスロコンを作成します.
研究 の 目的:
- LptDタンパク質の in vivo 酸化折り畳み経路を調査する.
- LptDの組立と機能におけるジスルファイド結合の役割を明らかにする.
- LptD成熟におけるLptEタンパク質の貢献を理解するために.
主な方法:
- LptDの折りたたみの中間物質のインビボ特性.
- ディスルファイド結合の形成と再配置の分析.
- LptD-LptE複合体の形成と機能を評価するための生化学的分析.
主要な成果:
- 酸化折り畳み経路におけるLptDの7つの異なるin vivo状態が特定されました.
- LptDの適切な組み立て中に,非原生ジルフイドを含む非機能的中間物質が観察されました.
- オキシダゼDsbAが中間生成に必要であり,LptEは原生ジスルファイド形式への成熟を誘発した.
結論:
- LptDのディスルファイド結合依存の折り畳みは,その機能にとって極めて重要です.
- LptD-LptE複合体の適切な組み立ては,二硫化物結合の再編成とLptD成熟のために不可欠です.
- この研究は,外膜タンパク質の折りたたみとバクテリアの複雑な組み立てのための新しいメカニズムを明らかにしています.
関連する概念動画
Formation of Lipopolysaccharides
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
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.
Bacterial Translocation and Protein Secretion
Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.


