PodcastStructural Biology

Science Signaling Podcast: 13 August 2013

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Science Signaling  13 Aug 2013:
Vol. 6, Issue 288, pp. pc21
DOI: 10.1126/scisignal.2004566

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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 Gβγ slows heart rate by allowing potassium ions to flow out of the cells. The structural basis of GIRK activation by Gβγ has been unclear because it has proven challenging to cocrystallize these proteins. Mahajan and Logothetis used multistage computational docking to predict the interactions between Gβγ and GIRK1 and then tested these predictions in Xenopus oocytes. These combined approaches yielded a model in which Gβγ occupies a cleft in GIRK1 to stabilize the open conformation of the channel. In addition to elucidating how Gβγ 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.

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