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In order to make good decisions, we use our knowledge and our reasoning. Often, this knowledge and reasoning is sound and solid. However, sometimes, we are swayed by biases or by others manipulating a situation. For example, let’s say you and three friends wanted to rent a house and had a combined target budget of $1,600. The realtor shows you only very run-down houses for $1,600 and then shows you a very nice house for $2,000. Might you ask each person to pay more in rent to get the...
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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
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  2. Dr5ドライブのトランスメブランアンカーの高次クラスタリング
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  2. Dr5ドライブのトランスメブランアンカーの高次クラスタリング

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DR5ドライブのトランスメブランアンカーの高次クラスタリング

Liqiang Pan1, Tian-Min Fu2, Wenbin Zhao3

  • 1Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute at Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.

Cell
|March 5, 2019

PubMed で要約を見る

まとめ
この要約は機械生成です。

デス受容体5 (DR5) 経膜ヘリクスは,無結合エクトドメインによる阻害を克服して,直接信号構造を組み立てる. リガンド結合またはエクトドメインの除去は,このクラスタリングと下流シグナリングを誘発する.

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科学分野:

  • 免疫学
  • 細胞生物学
  • 構造生物学

背景:

  • 免疫受容体のシグナル伝達には,受容体のクラスタリングが不可欠です.
  • このクラスタリングは以前は細胞外または細胞内相互作用を含むと考えられていた.

研究 の 目的:

  • 死亡受容体5 (DR5) の信号伝達におけるトランスメブランヘリックス (TMH) の役割を調査する.
  • DR5活性化とプリリガンド自己抑制のメカニズムを解明する.

主な方法:

  • DR5 TMHの核磁気共鳴 (NMR) 構造の決定
  • DR5 TMHのサイト指向型変異.
  • リガンド結合またはエクトドメイン除去時の下流信号活性化の分析.

主要な成果:

  • DR5 TMHだけで,信号伝送に不可欠な高次元の構造 (ダイマー-トリマーネットワーク) を形成することができます.
  • TMHの明確なトリメリゼーションとディメリゼーション面は,これらの相互作用を媒介する.
  • TMHトリメリゼーションまたは二酸化を妨げる突然変異は,リガンド誘発活性化を廃止する.
  • DR5エクトドメインのプロテオリスティックな除去は,リガンドなしでシグナリングを活性化します.

結論:

  • DR5の活性化には,プレリガンドの自己抑制を克服することによって引き起こされるTMHのクラスタリングが含まれます.
  • 結合されていないエクトドメインは,TMH媒介の受容体集合とシグナル伝達を阻害する.
  • リガンドまたは抗体の結合は,この抑制を解放し,TMHのクラスタリングと信号の開始を可能にします.