通过一种小分子对构造组合的调制,该分子抑制了参与细胞粘附的关键蛋白-蛋白相互作用
Akinobu Senoo1,2, Satoru Nagatoishi3,4, Daisuke Kuroda1,4,5
1Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Protein science : a publication of the Protein Society
|August 2, 2023
概括
这项研究引入了一种新的药物开发策略,通过调节蛋白质构成来准蛋白质-蛋白质相互作用. 这种方法提供了一种新的方法来抑制像P-cadherin这样的蛋白质介导的细胞粘附.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 调节蛋白质与蛋白质相互作用的小分子是有价值的药物候选物.
- 由于相互作用表面大,开发这种分子具有挑战性.
- 调节蛋白质构成组合是一种替代的抑制策略.
研究的目的:
- 研究调节蛋白质构成组合的小分子,以抑制蛋白质-蛋白质相互作用.
- 将这个概念应用于P-cadherin,P-cadherin是细胞粘附中的关键蛋白质.
主要方法:
- 用小分子抑制剂确定P-cadherin的晶体结构.
- 利用分子动力学模拟来理解抑制机制.
主要成果:
- 小分子抑制剂的机制涉及调节P-cadherin的结构组合.
- 这种调制导致细胞粘附的抑制.
结论:
- 改变蛋白质构成组合的小分子是抑制蛋白质-蛋白质相互作用的可行策略.
- 这种方法在开发治疗涉及异常细胞粘附的疾病的疗法方面具有潜在的应用.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
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
Cell Adhesion Molecules - Types and Functions
6.8K
Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily involved...
CAM Families
The Integrin family of proteins is primarily involved...
6.8K
Cell-matrix's Response to Mechanical Forces
2.7K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.7K
Immunoglobulin-like Cell Adhesion Molecules
3.3K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K


