互原子分析揭示了新型ALMS1-CEP70复合体与中心体集群的联系
Franziska Woerz1, Felix Hoffmann1, Shibu Antony1
1Eberhard Karls University Tübingen, Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
Molecular & cellular proteomics : MCP
|December 20, 2023
概括
使用内源标记细胞研究了阿尔斯特伦综合征蛋白1 (ALMS1) 相互作用. 鉴定了CEP70等新型相互作用体,揭示了ALMS1在乳毛和疾病中的功能.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 阿尔斯特罗姆综合征 (ALMS) 是一种罕见的遗传疾病,由ALMS1基因突变引起.
- ALMS1蛋白定位于基底体,并与信号通路有关,但其确切的功能尚不清楚.
- 研究蛋白相互作用对于理解ALMS1的分子作用至关重要.
研究的目的:
- 使用内源标记细胞识别与ALMS1相互作用的蛋白质.
- 调查ALMS1缺陷的功能后果,并确定新的相互作用体.
- 阐明ALMS1及其相互作用因子在纤毛功能和疾病中的作用.
主要方法:
- 在人类细胞中使用CRISPR/Cas9介导的ALMS1内源标记.
- 基于亲和性的蛋白质复合体分析,以确定ALMS1相互作用体.
- 在ALMS1缺乏细胞的功能研究和CEP70淘汰实验.
主要成果:
- 识别与ALMS1相互作用的中心体和微管相关蛋白质,包括CEP70.0.
- 缺少ALMS1导致眼缩短,而CEP70的减少则减少了基底体的ALMS1.
- CEP70的TPR-CT域特别与ALMS1相互作用,并且该域也结合了其他纤维蛋白,如CEP135.
结论:
- 对内源标记ALMS1的蛋白质复合体分析为其功能提供了洞察力.
- CEP70是ALMS1的新型相互作用者,在ALMS1的局部化和长度方面发挥作用.
- 这些发现为了解相关过程和疾病中的ALMS1和CEP70提供了候选清单.
相关概念视频
Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K
Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
Centrioles and Centrosomes
2.7K
Most animal cells comprise a pair of centrioles together called a centrosome. The cell duplicates its centrosome and contains two centrosomes side-by-side, which begin to move apart during the prophase. As the centrosomes migrate to two different sides of the cell, microtubules start extending from each centrosome toward the other end. The mitotic spindle is composed of the centrosomes and their emerging microtubules.
Near the end of the prophase, also called late prophase or...
Near the end of the prophase, also called late prophase or...
2.7K
Centrosome Duplication
4.0K
The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
4.0K
Assembly of Signaling Complexes
5.8K
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,...
5.8K
Cytoskeletal Accessory Proteins
3.1K
The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...
3.1K


