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Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy
Published on: March 5, 2017
Dissecting membrane insertion of mitochondrial beta-barrel proteins
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
Summary
Researchers discovered the universal sorting signal for mitochondrial beta-barrel proteins. This signal, the beta-signal, guides protein insertion into the SAM complex, enabling mitochondrial communication and cell viability.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitochondrial outer membrane communication relies on beta-barrel proteins.
- These proteins are synthesized in the cytosol and imported via the TOM and SAM machinery.
- The SAM complex, comprising Sam50 and Sam35, is crucial for cell viability.
Purpose of the Study:
- To identify the universal sorting signal of mitochondrial beta-barrel proteins.
- To elucidate the mechanism of precursor insertion and integration mediated by the SAM complex.
Main Methods:
- Identification of the sorting signal in mitochondrial beta-barrel proteins.
- Analysis of the interaction between the beta-signal, Sam35, and Sam50.
- Investigating the functional consequences of signal recognition on the Sam50 channel.
Main Results:
- A universal sorting signal, termed the beta-signal, was identified in mitochondrial beta-barrel proteins across eukaryotes.
- The beta-signal initiates precursor insertion into the SAM complex by forming a ternary complex with Sam35 and Sam50.
- Sam35 recognition of the beta-signal triggers a significant increase in Sam50 channel conductance, facilitating precursor release and lipid phase integration.
Conclusions:
- A two-stage mechanism for beta-barrel protein biogenesis is proposed, involving signal-driven insertion into a membrane protein complex followed by lipid phase integration.
- This mechanism may represent a general pathway for the biogenesis of all beta-barrel proteins.
- Understanding this pathway is vital for mitochondrial function and cellular communication.
Related Concept Videos
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
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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...
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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...
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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,...