Direct visualization of KirBac3.1 potassium channel gating by atomic force microscopy
Szymon Jarosławski1, Brittany Zadek, Frances Ashcroft
1Institut Curie, UMR168-CNRS, 26 Rue d'Ulm, 75248 Paris, France.
Journal of Molecular Biology
|October 16, 2007
Summary
Atomic force microscopy revealed how magnesium ions alter KirBac3.1 potassium channel structure. This ion binding causes conformational changes, constricting the cytoplasmic pore and impacting cell excitability.
Area of Science:
- Biophysics
- Structural Biology
- Membrane Protein Dynamics
Background:
- KirBac3.1 is a transmembrane potassium channel critical for regulating cell excitability.
- These channels are modulated by intracellular ligands, influencing their gating (opening and closing).
- Dysfunction in potassium channels is linked to various human diseases.
Purpose of the Study:
- To investigate the structural rearrangements of KirBac3.1 in response to magnesium (Mg2+) binding.
- To utilize high-resolution atomic force microscopy (AFM) as an interactive tool for studying potassium channel conformational changes.
Main Methods:
- High-resolution atomic force microscopy (AFM) was employed to image KirBac3.1 embedded in lipid bilayers.
- The cytoplasmic surface of the channel was visualized in the presence and absence of Mg2+.
Main Results:
- In the absence of Mg2+, KirBac3.1 subunits formed a dimer-of-dimers structure with a central depression.
- Upon Mg2+ addition, the intracellular domains rearranged, condensing into a single protrusion and increasing in height.
- Mg2+ binding led to the disappearance of the central cavity, indicating a constriction of the cytoplasmic pore.
Conclusions:
- Magnesium ions induce significant conformational changes in the intracellular ligand-binding domains of KirBac3.1.
- These structural alterations are likely transmitted to the transmembrane helices, affecting potassium channel gating.
- AFM provides a direct method for measuring protein surface conformational changes induced by ligand binding in ion channels.
