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Imaging CFTR: a tail to tail dimer with a central pore.
Hermann Schillers1, Victor Shahin, Lars Albermann
1Institute of Physiology II, Nanolab, University of Münster, Germany. schille@uni-muenster.de
Summary
Atomic force microscopy revealed the structure of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in native membranes. Two CFTR molecules form a dimer, creating a central pore essential for ion channel function.
Area of Science:
- Biophysics
- Molecular Biology
- Membrane Protein Structure
Background:
- The cystic fibrosis transmembrane conductance regulator (CFTR) is an ABC transporter crucial for ion transport.
- CFTR mutations cause cystic fibrosis, a genetic disorder.
- CFTR's role as an ion channel requires dimerization, but its native structure is unknown.
Purpose of the Study:
- To visualize and characterize the structural arrangement of CFTR in native plasma membranes.
- To determine the oligomeric state of CFTR essential for its ion channel function.
Main Methods:
- Utilized atomic force microscopy (AFM) on inside-out membrane patches from Xenopus laevis oocytes expressing CFTR.
- Employed cAMP stimulation and immunogold labeling with antibodies against CFTR's C-terminus.
- Scanned the intracellular surface of plasma membrane patches to identify CFTR structures.
Main Results:
- Detected ring-like structures with bipartite symmetry near immunogold labels.
- The observed ring substructure is consistent with a CFTR dimer model.
- AFM analysis indicated two CFTR molecules arranged in parallel, tail-to-tail, forming a central pore.
Conclusions:
- The study provides a structural model for the CFTR chloride channel in native membranes.
- The findings suggest a parallel, tail-to-tail dimeric arrangement of CFTR molecules.
- This configuration is proposed as the functional state of the CFTR ion channel.