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Related Concept Videos

Protein Transport into the Inner Mitochondrial Membrane01:34

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...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...

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Related Experiment Video

Updated: Jul 2, 2026

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
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The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

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The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23.

Kristen N Beverly1, Michael R Sawaya, Einhard Schmid

  • 1Department of Chemistry and Biochemistry, Box 951569, University of California, Los Angeles, CA 90095-1569, USA.

Journal of Molecular Biology
|August 19, 2008
PubMed
Summary

The Tim8-Tim13 complex chaperones mitochondrial proteins using a jellyfish-like structure with tentacle helices. This study reveals its molecular interactions with Tim23, crucial for mitochondrial protein import.

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Area of Science:

  • Mitochondrial biology
  • Protein import and translocation
  • Structural biology

Background:

  • The Tim8-Tim13 complex is vital for the TIM22 pathway, importing mitochondrial carrier proteins into the inner membrane.
  • Its precise structure and interaction with substrates like Tim23 are not well understood.
  • Understanding this complex is key to deciphering mitochondrial protein import mechanisms.

Purpose of the Study:

  • To elucidate the structural features of the yeast Tim8-Tim13 complex.
  • To characterize the binding interaction between the Tim8-Tim13 complex and its substrate Tim23.
  • To develop a molecular model for the chaperoned import of Tim23.

Main Methods:

  • X-ray crystallography was used to determine the structure of the yeast Tim8-Tim13 complex at 2.6 Å resolution.
  • Surface plasmon resonance (SPR) was employed to analyze the binding kinetics and stoichiometry between Tim8-Tim13 and Tim23.
  • Integration of structural and binding data to propose a molecular model.

Main Results:

  • The crystal structure revealed a hexameric complex with a central body and extending helical tentacles, similar to other chaperones.
  • SPR analysis indicated approximately six binding sites on the Tim8-Tim13 complex, with binding exhibiting positive cooperativity.
  • A molecular model suggests hydrophobic pockets at the helix-body junctions bind specific Tim23 sequences, while tentacle patches interact with transmembrane helices.

Conclusions:

  • The Tim8-Tim13 complex possesses a unique architecture facilitating substrate binding and translocation.
  • Its interaction with Tim23 is complex, involving multiple binding sites and cooperativity, essential for efficient mitochondrial import.
  • The findings provide insights into the molecular basis of protein transport across the mitochondrial intermembrane space.