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Additional file 8: Figure S8. of Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs

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posted on 2016-04-05, 05:00 authored by Gemma Navarro, Arnau Cordomí, Monika Zelman-Femiak, Marc Brugarolas, Estefania Moreno, David Aguinaga, Laura Perez-Benito, Antoni Cortés, Vicent Casadó, Josefa Mallol, Enric Canela, Carme Lluís, Leonardo Pardo, Ana García-Sáez, Peter McCormick, Rafael Franco
Evolution of TM4/5 and TM5/6 interfaces as devised from MD simulations of the adenosine A1R-A2AR heterotetramer in complex with Gi and Gs. (A) Representative snapshots (20 structures collected every 25 ns) of the TM domains of A1R bound to Gi (red), Gi-unbound A1R (orange), A2AR bound to Gs (dark green), and Gs-unbound A2AR (light green). TM helices 4 and 5 are highlighted in light blue and gray, respectively. Initial (at 0 ns, transparent cylinders) and final (at 500 ns, solid cylinders) snapshots of TM interfaces are shown for homodimerization (TM4/5, within rectangles) and heterodimerization (TM5/6, within a circle) bundles. TM helices 4 (light blue), 5 (gray), and 6 (orange and green) are highlighted. (B) Root-mean-square deviations (rmsd) on protein α-carbons of the four-helix bundles forming the TM5/6 interface (orange solid line), TM4/5 interface of A1R (blue dotted line), and TM4/5 interface of A2AR (blue solid line) throughout the MD simulation. (C) Contact maps of the TM4/5 interface (rectangles in panel A) in the A1R or A2AR homodimer (left and right panels) and of the TM5/6 interface (circle in panel A) in the A1R-A2AR heterodimer (middle panel). Darker dots show more frequent contacts. (D) Detailed view of the extensive network of hydrophobic interactions (mainly of aromatic side chains) within the TM4/5 (left and right panels) and TM5/6 (middle panel) interfaces. The amino acids are numbered following the generalized numbering scheme of Ballesteros and Weinstein [37, 38]. This allows easy comparison among residues in the 7TM segments of different receptors. (TIF 4004 kb)


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