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bioRxiv · 10.1101/2020.11.27.401265

A set of common movements within GPCR-G-protein complexes from variability analysis of cryo-EM datasets

Marino, J.·Schertler, G. F. X.
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Abstract

G-protein coupled receptors (GPCRs) are among the most versatile signal transducers in the cell. Once activated, GPCRs sample a large conformational space and couple to G-proteins to initiate distinct signaling pathways. The dynamical behavior of GPCR-G-protein complexes is difficult characterize structurally. Here, we report on the use of variability analysis to characterize the inherent flexibility within the cryo-EM dataset of the rhodopsin-Gi-protein complex (Tsai et al., 2019), on which this article builds on. We compare the outcome of this analysis with recently published results obtained on the cannabinoid-Gi- and secretin-Gs-receptor complexes. Despite differences related to the biochemical compositions of the three samples, a set of consensus movements emerges. We anticipate that systematic variability analysis on GPCR-G-protein complexes may provide useful information not only at the biological level, but also for improving the preparation of more stable samples for cryo-EM single-particle analysis.

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Marino, J., Schertler, G. F. X.. 2020-11-27. A set of common movements within GPCR-G-protein complexes from variability analysis of cryo-EM datasets. https://doi.org/10.1101/2020.11.27.401265

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