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相关概念视频

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

6.0K
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,...
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.6K
Protein-protein Interfaces02:04

Protein-protein Interfaces

13.8K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

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In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
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Protein-Protein Interfaces02:04

Protein-Protein Interfaces

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Matrix Proteoglycans and Glycoproteins01:21

Matrix Proteoglycans and Glycoproteins

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Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
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相关实验视频

Updated: Sep 19, 2025

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
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移植的卷状作为多价值架构用于蛋白质识别.

Amanda M Acevedo-Jake1, Bram Mylemans2, Danielle F Kay3

  • 1School of Chemistry, University of Birmingham, Edgbaston B15 2TT, U.K.

ACS chemical biology
|June 5, 2025
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概括

自组装提供了一种新的方法来抑制蛋白质与蛋白质相互作用 (PPI). 通过抑制MCL-1来开发向癌症疗法,Dimeric卷-卷轴支架显示出开发向癌症疗法的前景.

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Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
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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:

  • 自组装对于设计蛋白质与蛋白质相互作用 (PPI) 抑制剂非常有价值.
  • 抗瘤性蛋白质MCL-1是瘤学中的一个关键目标.
  • 卷轴螺旋脚手架为抑制器设计提供可调节的特性.

研究的目的:

  • 设计和评估可调节的卷轴螺旋脚手架作为MCL-1的抑制剂.
  • 调查寡合化,多价值性和合作性对PPI抑制的影响.
  • 探索这些支架在准阿尔法螺旋介导PPI方面的潜力.

主要方法:

  • 从NOXA-B中接种热点残留物到卷轴螺旋杆架上.
  • 创建同型和异型的卷曲-卷曲.
  • 使用生物物理方法评估抑制剂的效力和选择性.
  • 使用AlphaFold2进行结构建模.

主要成果:

  • 工程化二次卷-卷可以实现中纳米级强度和对MCL-1的选择性超过BCL-xL.
  • 观察到在同位体卷轴卷轴与MCL-1的结合中存在积极的合作性,稳定了双方的合作伙伴.
  • 高阶寡合体 (三元体,四元体) 显示抑制功效降低.
  • 确定了卷轴-卷轴寡合化和目标结合之间的复杂相互作用.

结论:

  • 在开发阿尔法螺旋介导PPI的抑制剂方面,二进制卷卷螺旋支架是最有效的.
  • 这项研究为设计针对MCL-1的新型基疗法提供了基础.
  • 了解寡合化的作用对于优化PPI抑制剂设计至关重要.