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Structural model of active Bax at the membrane
Stephanie Bleicken1, Gunnar Jeschke2, Carolin Stegmueller1
1Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart, Germany; German Cancer Research Center, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany; Interfaculty Institute of Biochemistry, Eberhard Karls University Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
Molecular Cell
|December 3, 2014
Summary
This study reveals the 3D structure of active Bax, a protein crucial for apoptosis. Active Bax forms dimer assemblies at the membrane, creating pores that release cytochrome c and initiate cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Biophysics
Background:
- Bax protein is essential for the mitochondrial pathway of apoptosis.
- Activation of Bax leads to mitochondrial outer membrane permeabilization and cell death.
- The precise structure and mechanism of membrane-inserted Bax remain poorly understood.
Purpose of the Study:
- To elucidate the 3D structure of active Bax at the membrane.
- To understand the mechanism of Bax-mediated mitochondrial permeabilization.
Main Methods:
- Double electron-electron resonance (DEER) spectroscopy.
- Liposomes and isolated mitochondria as model systems.
Main Results:
- A 3D model of active Bax at the membrane was proposed.
- Active Bax forms dimer assemblies on the mitochondrial surface.
- A flexible piercing domain and a clamp-like conformation of helices 5 and 6 were identified as key features for pore formation.
Conclusions:
- Active Bax functions as dimer assemblies, not monomers.
- The structural rearrangements, particularly the opening of helices 5 and 6, are critical for Bax's pro-apoptotic function.
- This provides new insights into the mechanism of mitochondrial outer membrane permeabilization.
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