Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-44594
Cell. September 30, 2011; 147 (1): 199-208.

Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.

Whorton MR , MacKinnon R .


Abstract
G protein-gated K(+) 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(+) 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(2) suggest that G proteins open only the G loop gate in the absence of PIP(2), but in the presence of PIP(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(+) ion-binding site, which would allow intracellular Na(+) to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.

PubMed ID: 21962516
PMC ID: PMC3243363
Article link: Cell.
Grant support: Howard Hughes Medical Institute , R01 GM043949-21 NIGMS NIH HHS , P30 EB009998 NIBIB NIH HHS

Genes referenced: kcnj3 kcnj5 kcnj6
Antibodies referenced:

My Xenbase: [ Log-in / Register ]
version: [3.2.2]


Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556