Inter- and intrasubunit interactions between transmembrane helices in the open state of P2X receptor channels
- Authors
- Heymann, G., Dai, J., Li, M., Silberberg, S.D., Zhou, H.X., and Swartz, K.J.
- ID
- ZDB-PUB-131105-9
- Date
- 2013
- Source
- Proceedings of the National Academy of Sciences of the United States of America 110(42): E4045-E4054 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Protein Structure, Tertiary
- Zebrafish
- Protein Structure, Secondary
- Adenosine Triphosphate/chemistry*
- Adenosine Triphosphate/genetics
- Adenosine Triphosphate/metabolism
- Receptors, Purinergic P2X4/chemistry*
- Receptors, Purinergic P2X4/metabolism
- Crystallography, X-Ray
- Models, Molecular*
- Animals
- PubMed
- 24082111 Full text @ Proc. Natl. Acad. Sci. USA
P2X receptor channels open in response to the binding of extracellular ATP, a property that is essential for purinergic sensory signaling. Apo and ATP-bound X-ray structures of the detergent-solubilized zebrafish P2X4 receptor provide a blueprint for receptor mechanisms but unexpectedly showed large crevices between subunits within the transmembrane (TM) domain of the ATP-bound structure. Here we investigate both intersubunit and intrasubunit interactions between TM helices of P2X receptors in membranes using both computational and functional approaches. Our results suggest that intersubunit crevices found in the TM domain of the ATP-bound crystal structure are not present in membrane-embedded receptors but substantiate helix interactions within individual subunits and identify a hot spot at the internal end of the pore where both the gating and permeation properties of P2X receptors can be tuned. We propose a model for the structure of the open state that has stabilizing intersubunit interactions and that is compatible with available structural constraints from functional channels in membrane environments.