Download MendeleyStructural Basis of Open Channel Block in a Prokaryotic Pentameric Ligand-Gated Ion Channel
Hilf, R.J.C., Bertozzi, C., Zimmermann, I., Reiter, A., Trauner, D., Dutzler, R.(2010) Nat Struct Mol Biol 17: 1330
- PubMed: 21037567
- DOI: https://doi.org/10.1038/nsmb.1933
- Primary Citation of Related Structures:
2XQ3, 2XQ4, 2XQ5, 2XQ6, 2XQ7, 2XQ8, 2XQ9, 2XQA - PubMed Abstract:
The flow of ions through cation-selective members of the pentameric ligand-gated ion channel family is inhibited by a structurally diverse class of molecules that bind to the transmembrane pore in the open state of the protein. To obtain insight into the mechanism of channel block, we have investigated the binding of positively charged inhibitors to the open channel of the bacterial homolog GLIC by using X-ray crystallography and electrophysiology. Our studies reveal the location of two regions for interactions, with larger blockers binding in the center of the membrane and divalent transition metal ions binding to the narrow intracellular pore entry. The results provide a structural foundation for understanding the interactions of the channel with inhibitors that is relevant for the entire family.
Organizational Affiliation:
Department of Biochemistry, University of Z¨¹rich, Z¨¹rich, Switzerland.
