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Sci. Signal., 13 August 2013
Vol. 6, Issue 288, p. pc21
[DOI: 10.1126/scisignal.2004566]


Science Signaling Podcast: 13 August 2013

Diomedes E. Logothetis1, Rahul Mahajan1, and Annalisa M. VanHook2

1 Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
2 Web Editor, Science Signaling, American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005, USA.

Abstract: This Podcast features an interview with Diomedes Logothetis and Rahul Mahajan, authors of a Research Article that appears in the 13 August 2013 issue of Science Signaling. In cardiomyocytes, activation of G protein–regulated inwardly rectifying potassium channels (GIRKs) by Gβ{gamma} slows heart rate by allowing potassium ions to flow out of the cells. The structural basis of GIRK activation by Gβ{gamma} has been unclear because it has proven challenging to cocrystallize these proteins. Mahajan and Logothetis used multistage computational docking to predict the interactions between Gβ{gamma} and GIRK1 and then tested these predictions in Xenopus oocytes. These combined approaches yielded a model in which Gβ{gamma} occupies a cleft in GIRK1 to stabilize the open conformation of the channel. In addition to elucidating how Gβ{gamma} promotes GIRK2 activation, this study also demonstrates an approach for combining computational and experimental methods to address protein-protein interactions when crystals of multiprotein complexes are not available.

Citation: D. E. Logothetis, R. Mahajan, A. M. VanHook, Science Signaling Podcast: 13 August 2013. Sci. Signal. 6, pc21 (2013).

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