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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
NATL ACAD SCIENCES, 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.108, No.38 [2011], p16086-16091
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
http://www.pnas.org/content/108/38/16086http://hdl.handle.net/20.500.11754/37391
ISSN
0027-8424
DOI
10.1073/pnas.1113645108
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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