SIR2エフェクターフィラメントアセンブリによるThoeris抗ウイルスシステムの活性化
Giedre Tamulaitiene1, Dziugas Sabonis2, Giedrius Sasnauskas2
1Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania. giedre.tamulaitiene@bti.vu.lt.
Nature
|February 21, 2024
まとめ
バクテリアはトエリスのような防御システムを用いて 細菌菌 (ファージ) 感染症と戦う. この研究では,サイクリックなADPリボース信号を結合すると,ThsAのThoerisエフェクタがフィラメントアセンブリを通じて活性化され,迅速なNAD+枯渇につながることを明らかにしています.
科学分野:
- 分子生物学
- 生物化学
- 構造生物学
背景:
- 細菌はウイルス感染と戦うために 洗練された抗菌体防御システムを持っています
- 注目すべき防御メカニズムであるThoerisシステムは,センサー (ThsB) とエフェクタ (ThsA) モジュールで構成されています.
- 構造データにもかかわらず,ThsAの活性化メカニズム,特に周期性分子 gcADPRとの相互作用は不明でした.
研究 の 目的:
- トエリスエフェクタ protein,ThsAの活性化メカニズムを解明する
- 合成された循環分子""'−3'グリコサイクルADPリボース (gcADPR) がThsAのエフェクタ機能をどのように誘発するかを決定する.
- 細菌の防御におけるThsA活性化とその役割の構造的基礎を理解する.
主な方法:
- 二次性ThsB'タンパク質を用いた1' - 3'gcADPRのインビトロ合成
- 活性化されたThsAの構造を決定するための冷凍電子顕微鏡 (cryo-EM)
- NAD+の水解とThsAフィラメント形成を評価する生化学的測定法.
主要な成果:
- 1' - 3' gcADPRは,ThsAのSLOGドメインと結合し,そのアクティベーションを開始する.
- 活性化されたThsAは,テトラメアの螺旋状フィラメントの組み立てを受けます.
- Cryo-EM構造は,フィラメントアセンブリが活性SIR2ドメイン構成を安定させ,迅速なNAD+枯渇を促進することを明らかにする.
- ThsAはgcADPRに対するスイッチのような反応を示し,フィラメント形成によって媒介される.
結論:
- バクテリアの防御タンパク質ThsAは,gcADPR結合によって活性化され,フィラメントの組み立てにつながります.
- フィラメント形成はThsAの活性構造を安定させ,効率的なNAD+水解を可能にします.
- 信号に依存するスイッチのようなメカニズムで 強力な抗菌体防御をします
関連する概念動画
01:39Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
02:53CRISPR and crRNAs
17.0K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.0K
02:30siRNA - Small Interfering RNAs
16.8K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.8K
01:19Actin Filament Depolymerization
3.1K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.1K
01:37The Unfolded Protein Response
4.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.6K
01:23RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K