结合LPS的酶激活和招募域 (CARDs) 是两部分的脂质结合模块
Anh B Cao1, Pascal Devant1, Chengliang Wang2
1Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Science advances
|March 7, 2025
概括
卡斯帕斯-11是一种
科学领域:
- 这是天生的免疫力.
- 分子生物学分子生物学
- 结构生物学是结构生物学.
背景情况:
- 卡斯巴酶-11在先天免疫中充当模式识别受体 (PRR).
- 它通过其 caspase 激活和招募域 (CARD) 识别细胞质细菌脂聚糖 (LPS) 和真核 (自我) 脂质.
- 通过caspase-11检测自我和非自我脂质的机制仍然不清楚.
研究的目的:
- 研究卡斯帕-11 CARD与自我和非自我脂质相互作用的分子机制.
- 为了确定是否涉及到CARD内部的共同或独特的约束区域.
- 基于这些发现,设计一个新的LPS结合域.
主要方法:
- 生物化学测定 生物化学测定
- 计算建模计算建模
- 基于细胞的测定.
- 对CARD领域的结构分析.
主要成果:
- 卡斯帕酶-11 CARD 作为一个双重的脂质结合模块.
- 在CARD中的特定区域与酸盐组和长酸链的自我和非自我脂质结合.
- 自身脂质结合在各种caspase-11同类和orthologs中保持.
- 一个新的LPS结合域是使用*Amphilophus citrinellus*的祖先CARD类域进行的.
结论:
- 这些发现阐明了通过caspase-11识别LPS的分子基础.
- 卡斯巴-11利用不同的区域来结合自我和非自我脂质,揭示了一个双重机制.
- 这项研究强调了自我脂质识别的保存性质,并为设计新型脂质结合域提供了一个框架.
相关概念视频
Caspases
11.8K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
11.8K
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Cytoskeletal Linker Proteins - Plakins
2.2K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.2K
Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K
Lipids as Anchors
5.5K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.5K
Regulation of Nuclear Protein Sorting
2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K


