ミトコンドリアのタンパク質インポート受容体Tom2020によるプレシーケンスの認識の構造的基礎

Y Abe¹, T Shodai, T Muto

¹Department of Structural Biology, Biomolecular Engineering Research Institute, Suita, Osaka, Japan.

Cell

|March 18, 2000

まとめ

ミトコンドリアタンパク質の輸入は,Tom20のような受容体に依存しています. この研究は,Tom2020を明らかにしています.

科学分野:

ミトコンドリア生物学ミトコンドリア生物学
タンパク質の輸入メカニズム
構造生物学構造生物学とは

背景:

ほとんどのミトコンドリアタンパク質は,サイトゾールで合成されます.
これらのタンパク質は,ミトコンドリアインポートのためのN端前列をもっています.
Tom20は,これらの前駆体タンパク質の一般的な受容体として作用します.

研究の目的:

ネズミのTom20受容体の構造を決定するために.
Tom20とプレシーケンスのペプチドの相互作用を明らかにするために.
ミトコンドリアタンパク質の分子基盤を理解するために.

主な方法:

核磁共振 (NMR) スペクトロスコーピーは,核磁共振 (NMR) スペクトロスコーピーを用います.
タンパク質前列複合体の構造分析
結合相互作用の生化学的特徴づけ

主要な成果:

ネズミのトム20の細胞領域は,アルファヘリクルの構造を形成する.
Tom20 の内部にある溝は,プレシーケンスのペプチドを収納しています.
プレシーケンスのペプチドは,輸入のための陽性電荷の重要な役割にもかかわらず, Tom20への結合を媒介する水害性相互作用により,アンフィフィリックヘリケルの構造を採用します.

結論:

Tom20前列複合体の構造は,ミトコンドリアタンパク質の輸入に関する洞察を提供します.
排水性相互作用は, Tom20へのプレシーケンスの結合の鍵です.
これらの相互作用を理解することは,ミトコンドリアのタンパク質ターゲティングの解読に不可欠です.

さらに関連する動画

08:55

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

Published on: July 19, 2021

09:01

Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria

Published on: January 7, 2022

関連する概念動画

01:39

Mitochondrial 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...

01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...

01:19

Translocation 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,...

01:37

Energy to Drive Translocation

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.
Generally, polypeptides are unfolded by two distinct...

01:34

Protein 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...

01:21

Structure 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...

関連する実験動画