感覚受容体における全般的な柔軟性:部位指向のクロスリンクアプローチ

J J Falke, D E Koshland

Science (New York, N.Y.)

|September 25, 1987

まとめ

バクテリアのアスパルテート受容体は,信号を送信するために構造的な柔軟性を利用します. リガンド結合は,受容体の全体的な変化を引き起こします.

科学分野:

バイオケミストリーバイオケミストリー
分子生物学は分子生物学である.
微生物学微生物学とは

背景:

アスパルテート受容体は,Escherichia coliやSalmonella typhimuriumなどのバクテリアの細胞表面における重要な感受伝達器である.
細胞外アスパルテート結合に反応して,細胞膜の信号伝導を媒介する.

研究の目的:

アスパルテート受容体の柔軟性とアロステリックメカニズムを研究する.
リガンド結合によって誘発されるダイナミックな構造変化を調査する.

主な方法:

7つの変異した受容体の構築,それぞれ特定の位置に単一のシステイン残留物を持っています.
サルフヒドリル基をクロスリンクサイトとして利用して,受容体オリゴマー内の分子内二硫化物結合を形成する.
ディスルファイド結合形成による構造変動とリガンド誘発の構成変化を分析する.

主要な成果:

変異体受容体における二硫化物結合形成は,構造的変動を成功裏に閉じ込めました.
ディスルファイド結合の形成は,リガンド誘発構造変化の検出を可能にしました.
証拠によると,受容体オリゴーマーには柔軟でダイナミックな構造があります.

結論:

アスパルテート受容体は,構造的に有意な柔軟性と動的行動を示す.
アスパルテート結合は,受容体オリゴマーの全体的な構造変化を誘導し,そのアロステル性特性を強調します.

さらに関連する動画

11:33

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

関連する概念動画

01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...

00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...

01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...

01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

関連する実験動画