ミトコンドリアのベータバレルタンパク質の解剖膜挿入
Stephan Kutik1, Diana Stojanovski, Lars Becker
1Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Universität Freiburg, Freiburg 79104, Germany; Fakultät für Biologie, Universität Freiburg, Freiburg 79104, Germany.
Cell
|March 25, 2008
まとめ
研究者らは,ミトコンドリアのベータ・バレルタンパク質の普遍的な分類信号を発見した. この信号,ベータ信号は,SAM複合体へのタンパク質挿入を誘導し,ミトコンドリアの通信と細胞活性を可能にします.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ミトコンドリア外膜の通信はベータバレルタンパク質に依存しています.
- これらのタンパク質はサイトゾールで合成され,TOMおよびSAM機構を通じて輸入されます.
- Sam50とSam35を構成するSAM複合体は,細胞の生存能力にとって極めて重要です.
研究 の 目的:
- ミトコンドリアのベータ・バレルタンパク質の普遍的分類信号を特定する.
- SAM複合体によって媒介される前駆体挿入と統合のメカニズムを解明する.
主な方法:
- ミトコンドリアのベータバレルタンパク質における分類信号の識別.
- ベータ信号,Sam35,Sam50.の相互作用の分析
- Sam50チャンネルでの信号認識の機能的影響を調査する.
主要な成果:
- ベータ信号と呼ばれる普遍的な分類信号は,真核生物のミトコンドリアのベータバレルタンパク質で特定されました.
- ベータ信号は,Sam35とSam50と三元複合体を形成することによって,SAM複合体への前駆体挿入を開始します.
- ベータ信号のSam35認識はSam50チャネル伝導率を大幅に増加させ,前駆体放出と脂質相統合を促進します.
結論:
- ベータ・バレルタンパク質バイオゲネシスの2段階のメカニズムが提案されており,それはシグナル駆動による膜タンパク質複合体への挿入を伴うもので,その後に脂質相統合が続く.
- このメカニズムは,すべてのベータバレルタンパク質の生体生成の一般的な経路を表す可能性があります.
- この経路を理解することは,ミトコンドリアの機能と細胞のコミュニケーションに不可欠です.
関連する概念動画
01:12Porin Insertion in the Outer Mitochondrial Membrane
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
01:21Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
01:09Multi-pass Transmembrane Proteins and β-barrels
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 G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
01:39Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
01:34Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...