安基林B与NrCAM和β2光谱的结构相互作用
bioRxiv : the preprint server for biology
|July 14, 2025
概括
自闭症谱系障碍 (ASD) 基因Ank2突变破坏了Ankyrin B (AnkB) 与NrCAM和β2-Spectrin的相互作用,影响了神经脊柱修剪和ASD病因.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 安基林B (AnkB) 是由Ank2基因编码的,这是一个高自信自闭症谱系障碍 (ASD) 基因.
- 220kDal AnkB异型通过L1-CAMs和Semaphorins调节树突脊柱的修剪,这对新皮层刺激平衡至关重要.
研究的目的:
- 通过使用AlphaFold进行结构模型,以分析Ankyrin B (AnkB) 与神经质相关的L1-CAM (NrCAM) 和β2-谱的相互作用.
- 通过突变发生和共免疫沉试验来验证这些模型.
- 研究与ASD相关的AnkB突变对蛋白质相互作用和神经元功能的影响.
主要方法:
- 用AlphaFold分子建模来预测使用NrCAM和β2-Spectrin的AnkB复杂结构.
- AnkB的局部定向突变,以破坏预测的相互作用场所.
- 在HEK293细胞中进行共免疫沉降测定,以评估蛋白质与蛋白质之间的相互作用.
- 评估AnkB A368G突变对Semaphorin 3F诱导的小鼠皮层神经元中脊柱修剪的影响.
主要成果:
- AlphaFold模型揭示了对NrCAM结合 (FIGQY动机) 和β2-光谱相互作用 (重复14-15) 的关键AnkB残留物.
- 与ASD相关的突变AnkB A368G和AnkB R977Q分别影响了对NrCAM和β2-谱的结合.
- 在培养的小鼠神经元中,AnkB A368G突变破坏了Semaphorin 3F诱导的脊柱修剪.
结论:
- 提供了对L1-CAM/AnkB复合体和β2-谱相互作用的结构洞察.
- 与ASD相关的AnkB误解突变可以破坏关键蛋白质相互作用.
- 这些干扰为与Ank2突变相关的ASD病因提供了分子基础.
相关概念视频
Structure of Cadherins
3.6K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.6K
Anchoring Junctions
4.0K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
4.0K
Assembly of Signaling Complexes
5.9K
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,...
5.9K
Formation of Higher-order Actin Filaments
3.1K
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
The high-order actin...
3.1K
Tension Response at Adherens Junctions
2.9K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.9K
Catenins
2.4K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.4K


