HIV-ヒトのタンパク質複合体のグローバルランドスケープ
Stefanie Jäger1, Peter Cimermancic, Natali Gulbahce
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
Nature
|December 23, 2011
まとめ
研究者らは,ヒト免疫不全ウイルス (HIV) のタンパク質と宿主細胞の相互作用をマッピングした. この研究は,HIVとヒトのタンパク質の相互作用497を特定し,保存された宿主標的と潜在的な複製阻害剤を明らかにしました.
科学分野:
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- ヒト免疫不全ウイルス (HIV) は,その有限なゲノムにより,複製のために宿主細胞機械に依存しています.
- ホストと病原体の相互作用を理解することは,ウイルスの複製戦略を解読し,介入策を開発するための鍵です.
研究 の 目的:
- 全18のHIV-1タンパク質と宿主タンパク質の間の物理的相互作用を体系的に特定する.
- 感染中にHIVによって宿主細胞機械の再配線を包括的にマッピングする.
主な方法:
- HIV宿主タンパク質複合体を捕捉するために,アフィニティタグと浄化質量スペクトロメトリーを使用した.
- 高い信頼性の相互作用を特定するために,定量的スコアシステム,MiSTが開発されました.
- 実験は,より広範な適用性のために,2つの異なるヒト細胞系 (HEK293とJurkat) で実施されました.
主要な成果:
- ヒトのタンパク質とヒトのタンパク質の相互作用の497の高信頼性が特定され,435のユニークなヒトタンパク質が関与しました.
- これらの相互作用の約40%は,テストされた両方の細胞タイプで保存された.
- HIVと相互作用する特定された宿主タンパク質,特に霊長類に保存されているものは,しばしばウイルスの複製を抑制することに関与しています.
結論:
- この研究は,HIVと宿主タンパク質の相互作用の詳細な地図を提供し,細胞プロセスのウイルス操作を理解するために不可欠です.
- HIV複製を阻害する宿主タンパク質の発見は,新しい治療戦略のための潜在的なターゲットを提供します.
- 乗っ取られた宿主タンパク質の保存された性質は,進化的圧力とウイルスのライフサイクルにおける潜在的な脆弱性を示唆しています.
関連する概念動画
01:57Protein Complexes with Interchangeable Parts
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 to...
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 to...
01:57Protein Complexes with Interchangeable Parts
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 to...
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 to...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
02:04Protein-protein Interfaces
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 polypeptide...
02:04Protein-Protein Interfaces
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 polypeptide...