Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium
- Rockefeller
G protein-gated K{sup +} channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K{sup +} channel. By comparing the wild-type structure to that of a constitutively active mutant, we identify a global conformational change through which G proteins could open a G loop gate in the cytoplasmic domain. The structures of both channels in the absence and presence of PIP{sub 2} suggest that G proteins open only the G loop gate in the absence of PIP{sub 2}, but in the presence of PIP{sub 2} the G loop gate and a second inner helix gate become coupled, so that both gates open. We also identify a strategically located Na{sup +} ion-binding site, which would allow intracellular Na{sup +} to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- UNIVERSITY
- OSTI ID:
- 1027666
- Journal Information:
- Cell, Vol. 147, Issue 1; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- ENGLISH
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