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Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein
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García-Nafría, Javier, Lee, Yang, Bai, Xiaochen, Carpenter, Byron and Tate, Christopher G. (2018) Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein. eLife, 2018 (7). e35946. doi:10.7554/eLife.35946
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Official URL: http://dx.doi.org/10.7554/eLife.35946
Abstract
The adenosine A2A receptor (A2AR) is a prototypical G protein-coupled receptor (GPCR) that couples to the heterotrimeric G protein GS. Here, we determine the structure by electron cryo-microscopy (cryo-EM) of A2AR at pH 7.5 bound to the small molecule agonist NECA and coupled to an engineered heterotrimeric G protein, which contains mini-GS, the βγ subunits and nanobody Nb35. Most regions of the complex have a resolution of ~3.8 Å or better. Comparison with the 3.4 Å resolution crystal structure shows that the receptor and mini-GS are virtually identical and that the density of the side chains and ligand are of comparable quality. However, the cryo-EM density map also indicates regions that are flexible in comparison to the crystal structures, which unexpectedly includes regions in the ligand binding pocket. In addition, an interaction between intracellular loop 1 of the receptor and the β subunit of the G protein was observed.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | G proteins, Ligand binding (Biochemistry) | |||||||||||||||
| Journal or Publication Title: | eLife | |||||||||||||||
| Publisher: | eLife Sciences Publications Ltd. | |||||||||||||||
| ISSN: | 2050-084X | |||||||||||||||
| Official Date: | 4 May 2018 | |||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 22 May 2018 | |||||||||||||||
| Volume: | 2018 | |||||||||||||||
| Number: | 7 | |||||||||||||||
| Article Number: | e35946 | |||||||||||||||
| DOI: | 10.7554/eLife.35946 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||
| RIOXX Funder/Project Grant: |
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