艰难 Clostridioides 转移酶 A 组件的 N 末端指导毒素活性和功效
Robin M Mullard1, Michael J Sheedlo1
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
mBio
|November 29, 2024
概括
一个新发现的KDKEK动机对于Clostridioides difficile转移酶 (CDT) 毒素的功能至关重要. 这一发现为CDT如何进入宿主细胞提供了一个模型,有助于理解C. difficile感染机制.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 艰难闭膜炎感染 (CDI) 是医院获得的腹的主要原因.
- CDI病理是由细菌毒素介导的,包括C. difficile转移酶 (CDT).
- CDT与严重的症状,增加的再感染和死亡率有关,但其中毒机制尚不清楚.
研究的目的:
- 为了阐明CDT中毒的机制.
- 为了确定CDT毒素的关键功能区域.
- 开发研究CDT在感染中的作用的工具.
主要方法:
- 鉴定一种保存的酸性/性残留基因 (KDKEK),这对于CDT功能至关重要.
- 低温电子显微镜 (Cryo-EM) 用于确定毒素的结构和动图方向.
- 产生非中毒的CDT突变体.
主要成果:
- 确定了一种KDKEK动机对于CDT毒素活性至关重要.
- 冷EM揭示了KDKEK基因的特定方向,这表明它在毒素输送中发挥了作用.
- 突变物被创造出来,可以组装,但不会毒害细胞.
结论:
- 该KDKEK动机及其方向对于启动CDT进入宿主细胞至关重要.
- 这种机制模型可能适用于其他细菌毒素.
- 非中毒的CDT突变将成为未来对CDI病原学的研究中宝贵的工具.
相关概念视频
Transcription Attenuation in Prokaryotes
15.1K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.1K
Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
Insertion of Single-pass Transmembrane Proteins in the RER
6.6K
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...
6.6K
Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Transfer RNA Synthesis
11.9K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K
Fusion of Secretory Vesicles with the Plasma Membrane
11.0K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.0K


