English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Position of transmembrane Helix 6 determines receptor G protein coupling specificity.

MPS-Authors
/persons/resource/persons15155

Grubmüller,  H.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

External Ressource
Fulltext (public)

2056641.pdf
(Publisher version), 2MB

Supplementary Material (public)

2056641_Suppl.pdf
(Supplementary material), 4MB

Citation

Rose, A. S., Elgeti, M., Zachariae, U., Grubmüller, H., Hofmann, K. P., Scheerer, P., et al. (2014). Position of transmembrane Helix 6 determines receptor G protein coupling specificity. Journal of the American Chemical Society, 136(32), 11244-11247. doi:10.1021/ja5055109.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0023-CE72-E
Abstract
G protein coupled receptors (GPCRs) transmit extracellular signals into the cell by binding and activating different intracellular signaling proteins, such as G proteins (Gαβγ, families Gi, Gs, Gq, G12/13) or arrestins. To address the issue of Gs vs Gi coupling specificity, we carried out molecular dynamics simulations of lipid-embedded active β2-adrenoceptor (β2AR*) in complex with C-terminal peptides derived from the key interaction site of Gα (GαCT) as surrogate of Gαβγ. We find that GiαCT and GsαCT exploit distinct cytoplasmic receptor conformations that coexist in the uncomplexed β2AR*. The slim GiαCT stabilizes a β2AR* conformation, not accessible to the bulkier GsαCT, which requires a larger TM6 outward tilt for binding. Our results suggest that the TM6 conformational heterogeneity regulates the catalytic activity of β2AR* toward Gi or Gs.