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Related Concept Videos

Tail-anchoring of Proteins in the ER Membrane01:45

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
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ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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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.
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Related Experiment Video

Updated: Sep 23, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
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Reconstitution of Msp1 Extraction Activity with Fully Purified Components

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Conserved structural elements specialize ATAD1 as a membrane protein extraction machine.

Lan Wang1,2, Hannah Toutkoushian1,2, Vladislav Belyy1,2

  • 1Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, United States.

Elife
|May 13, 2022
PubMed
Summary
This summary is machine-generated.

The mitochondrial protein ATAD1 (ATPases Associated with diverse cellular Activities) uses specific aromatic amino acids to remove mislocalized proteins, maintaining mitochondrial function. These aromatic residues are crucial and cannot be replaced by aliphatic ones.

Keywords:
AAA proteinsE. colicell biologycryo-EMhumanmitochondriamolecular biophysicsprotein mislocalizationprotein quality controlstructural biologytail-anchored proteins

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Area of Science:

  • Mitochondrial biology
  • Protein quality control
  • Molecular mechanisms of AAA+ proteins

Background:

  • Mitochondrial AAA protein ATAD1 maintains proteostasis by removing mislocalized membrane proteins.
  • The structural basis and energetic challenges of ATAD1's substrate extraction were previously unclear.
  • Previous studies revealed Msp1 (yeast ATAD1) uses aromatic amino acids to bind substrates.

Purpose of the Study:

  • To elucidate the structure and function of human ATAD1 in complex with a peptide substrate.
  • To investigate the role of aromatic amino acids in ATAD1's substrate binding and extraction mechanism.
  • To identify structural features that enable ATAD1's specific function in mitochondrial protein import.

Main Methods:

  • Determined cryo-electron microscopy (cryo-EM) structures of human ATAD1 with a peptide substrate at near atomic resolution.
  • Developed a microscopy-based assay to assess ATAD1 activity in live cells by monitoring protein mislocalization.
  • Performed functional assays to test the necessity of aromatic amino acids in ATAD1's pore-loop 1.

Main Results:

  • Human ATAD1 shares conserved structural elements and AAA protein mechanisms but possesses unique features.
  • Aromatic amino acids in ATAD1's pore-loop 1 are essential for its function and not substitutable by aliphatic residues.
  • A C-terminal α-helix significantly promotes ATAD1 oligomerization, distinguishing it from related proteins.

Conclusions:

  • Human ATAD1 utilizes specific aromatic amino acids for substrate interaction, crucial for its role in mitochondrial proteostasis.
  • The study clarifies ATAD1's mechanism for extracting hydrophobic proteins from the mitochondrial outer membrane.
  • Structural insights reveal ATAD1's unique adaptations for maintaining mitochondrial protein import capacity.