Structural Insights into the Process of GPCR-G Protein Complex Formation

Abstract

Highlights d An active b2AR structure was obtained by fusion with residues 381-394 of Gs (GsCT) d GsCT interacts with the b2AR differently compared with the b2AR-Gs complex structure d The structure of Gs GDP reveals the conformation of GsCT before b2AR engagement d A model for the initial stages of b2AR-Gs complex formation is proposed

Investigation on precision and performance for hot gas forming of thin-walled components of Ti2AlNb-based alloy

“…Apparently, the maximum thickness thinning occurred in the transition region between straight region and round region, which also verified the thickness distribution achieved in simulation. Due to the friction on the straight region, the transition region primely satisfies plastic yielding condition and produces compressive strain through the thickness [9]. From the comparison of thickness thinning ratio for the quadrate tubes formed at different temperatures, it is noted that the biggest fluctuation of wall thickness appeared in the tube formed at 950 °C due to the significant strain softening.…”

Ric‐8A, a GEF, and a Chaperone for G Protein α‐Subunits: Evidence for the Two‐Faced Interface

“…The model was generated by superimposition of the α5‐helix residues Gα t 335‐340 from Gα t GDP (PDB 1TAG) and the Ric‐8A1‐492/MBP‐Gα t 327‐350 structure (PDB 6N85), followed by rotation of 180° about the α‐helix axis. This rotation switches the Ric‐8A‐interacting side of the Gα t α5‐helix to that paralleled by the proposed intermediate G s /β2AR complex . Ric‐8A in green, the RD and HD of Gα t GDP are in orange and gray, respectively, the α5‐helix of Gα t in magenta.…”

“… Gα s E392 and R389 are surface exposed in heterotrimeric G s and available for the initial coupling with β2AR . The nucleotide‐binding site may already be destabilized in the intermediate complex due to disruption of the interactions between the C‐terminal portion of the α5 helix and the αN‐β1 loop in Gα s , thus promoting further transition to a stable nucleotide‐free complex conformation . Yet another intermediate state termed non‐canonical (NC) has been structurally described for the complex neurotensin receptor 1 with heterotrimeric G i .…”

Structural insights into ligand efficacy and activation of the glucagon receptor

“…4b). However, superimposition of the inactive GDP-bound G s heterotrimer 28 onto the nucleotide-free G s in the complex suggests that the bent α5 helix of the GDP-bound G protein (α5 GDP ) together with the known inherent flexibility of its very C-terminal end 29,30 , might allow the initial engagement of the GDP-bound G protein without outward displacement of TM6 (Fig. 4b).…”

“…Comparison of GDP-bound Gα s (green, PDB 6EG8) 28 and nucleotide-free Gα s (yellow) in complex with GCGR (cyan) showing differences in the α1 helix, α5 helix, and α5-β6 loop as well as in the α-helical domain upon binding to the receptor. b, The initial α5 engagement of GDP-bound Gα s (green) to GCGR with an inwardly positioned TM6 (orange, PDB 5YQZ) appears to be possible without the outward movement of TM6.…”