Structural flexibility of the Gas alpha-helical domain in the beta(2)-adrenoceptor Gs complex
- Title
- Structural flexibility of the Gas alpha-helical domain in the beta(2)-adrenoceptor Gs complex
- Author
- 채필석
- Keywords
- G protein-coupled receptor; negative stain electron microscopy; random conical tilt
- Issue Date
- 2011-09
- Publisher
- National Academy of Sciences
- Citation
- Proceedings of the National Academy of Sciences of the United States of America, v. 108, NO. 38, Page. 16086-16091
- Abstract
- The active-state complex between an agonist-bound receptor and a guanine nucleotide-free G protein represents the fundamental signaling assembly for the majority of hormone and neurotransmitter signaling. We applied single-particle electron microscopy (EM) analysis to examine the architecture of agonist-occupied beta(2)-adrenoceptor (beta(2)AR) in complex with the heterotrimeric G protein Gs (G alpha s beta gamma). EM 2D averages and 3D reconstructions of the detergent-solubilized complex reveal an overall architecture that is in very good agreement with the crystal structure of the active-state ternary complex. Strikingly however, the alpha-helical domain of G alpha s appears highly flexible in the absence of nucleotide. In contrast, the presence of the pyrophosphate mimic foscarnet (phosphonoformate), and also the presence of GDP, favor the stabilization of the alpha-helical domain on the Ras-like domain of G alpha s. Molecular modeling of the alpha-helical domain in the 3D EM maps suggests that in its stabilized form it assumes a conformation reminiscent to the one observed in the crystal structure of G alpha s-GTP gamma S. These data argue that the alpha-helical domain undergoes a nucleotide-dependent transition from a flexible to a conformationally stabilized state.
- URI
- https://www.pnas.org/doi/full/10.1073/pnas.1113645108https://repository.hanyang.ac.kr/handle/20.500.11754/176155
- ISSN
- 0027-8424;1091-6490
- DOI
- 10.1073/pnas.1113645108
- Appears in Collections:
- COLLEGE OF ENGINEERING SCIENCES[E](공학대학) > BIONANO ENGINEERING(생명나노공학과) > Articles
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