クロストリジウム・ディフィッシル毒素Bによる状タンパク質の認識のための構造的基礎
Peng Chen1, Liang Tao2, Tianyu Wang1
1Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Science (New York, N.Y.)
|May 12, 2018
まとめ
クロストリジウム・ディフィシル・トキシンBは,脂肪酸共受容体を使って,Frizzled受容体と結合する. この相互作用はWnt信号を遮断し,C. difficile感染の治療のための新しい標的を明らかにします.
科学分野:
- 構造生物学
- 病気 の 分子 機構
- 微生物学
背景:
- クロストリジウム・ディフィシル感染 (CDI) は,抗生物質関連下痢の主な原因です.
- 主要な毒性因子であるClostridium difficile毒素B (TcdB) は,Frizzled (FZD) Wnt受容体を通して結腸内皮質を標的とする.
- FZDのTcdB認識の正確なメカニズムはほとんど不明である.
研究 の 目的:
- TcdBがFrizzled受容体に結合する構造的基礎を解明する.
- TcdB-FZDの相互作用における共受容体の役割を理解する.
- CDIにおけるWnt信号を標的とした潜在的な治療戦略を特定する.
主な方法:
- ヒトFZD2のシステインに富んだ領域に結合したTcdB断片の構造をX線結晶学で決定した.
- 高解像度構造分析 2.5 アングストームで
- Wnt結合とシグナル伝達阻害を評価する生化学的測定法
主要な成果:
- 結晶構造は,FZD2に結合した内生脂肪酸を明らかにし,TcdBの重要な共受容体として作用した.
- この脂質は,Wnt関連パルミトール酸が通常結合する部位を占め,Wntの結合を防ぐ.
- TcdB結合は脂肪酸を効果的に隔離し,FZD媒介のWnt信号を阻害する.
結論:
- 脂肪酸はFZD媒介のTcdBの病原性において重要な役割を果たします.
- TcdBは脂肪酸共受容体のメカニズムを使用して,Wnt信号を妨害します.
- これらの発見は,Wntシグナル伝達経路を調節することによって,Clostridium difficile感染に対する治療的介入のための新しい戦略を提供します.
関連する概念動画
02:15Protein and Protein Structure
88.6K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
88.6K
01:56Structural Protein Function
30.0K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
30.0K
01:56Structural Protein Function
3.3K
3.3K
02:15Protein and Protein Structures
19.3K
19.3K
01:36Types of Toxins
3.7K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
3.7K
02:22Structures of Solids
18.0K
Solids in which the atoms, ions, or molecules are arranged in a definite repeating pattern are known as crystalline solids. Metals and ionic compounds typically form ordered, crystalline solids. A crystalline solid has a precise melting temperature because each atom or molecule of the same type is held in place with the same forces or energy. Amorphous solids or non-crystalline solids (or, sometimes, glasses) which lack an ordered internal structure and are randomly arranged. Substances that...
18.0K