Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model.
Agonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a...
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doaj-b5a4b82eefdf42ee9740f977fd4092542020-11-25T01:24:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e015952810.1371/journal.pone.0159528Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model.Min Hyeok KimYoung Jin KimHee Ryung KimTae-Joon JeonJae Boong ChoiKa Young ChungMoon Ki KimAgonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a GDP-bound G protein heterotrimer. The G protein cycle is allosterically modulated by conformational changes of the Gα subunit. Although biochemical and biophysical methods have elucidated the structure and dynamics of Gα, the precise conformational mechanisms underlying the G protein cycle are not fully understood yet. Simulation methods could help to provide additional details to gain further insight into G protein signal transduction mechanisms. In this study, using the available X-ray crystal structures of Gα, we simulated the entire G protein cycle and described not only the steric features of the Gα structure, but also conformational changes at each step. Each reference structure in the G protein cycle was modeled as an elastic network model and subjected to normal mode analysis. Our simulation data suggests that activated receptors trigger conformational changes of the Gα subunit that are thermodynamically favorable for opening of the nucleotide-binding pocket and GDP release. Furthermore, the effects of GTP binding and hydrolysis on mobility changes of the C and N termini and switch regions are elucidated. In summary, our simulation results enabled us to provide detailed descriptions of the structural and dynamic features of the G protein cycle.http://europepmc.org/articles/PMC4970668?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Min Hyeok Kim Young Jin Kim Hee Ryung Kim Tae-Joon Jeon Jae Boong Choi Ka Young Chung Moon Ki Kim |
spellingShingle |
Min Hyeok Kim Young Jin Kim Hee Ryung Kim Tae-Joon Jeon Jae Boong Choi Ka Young Chung Moon Ki Kim Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. PLoS ONE |
author_facet |
Min Hyeok Kim Young Jin Kim Hee Ryung Kim Tae-Joon Jeon Jae Boong Choi Ka Young Chung Moon Ki Kim |
author_sort |
Min Hyeok Kim |
title |
Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. |
title_short |
Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. |
title_full |
Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. |
title_fullStr |
Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. |
title_full_unstemmed |
Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model. |
title_sort |
computational simulation of the activation cycle of gα subunit in the g protein cycle using an elastic network model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Agonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a GDP-bound G protein heterotrimer. The G protein cycle is allosterically modulated by conformational changes of the Gα subunit. Although biochemical and biophysical methods have elucidated the structure and dynamics of Gα, the precise conformational mechanisms underlying the G protein cycle are not fully understood yet. Simulation methods could help to provide additional details to gain further insight into G protein signal transduction mechanisms. In this study, using the available X-ray crystal structures of Gα, we simulated the entire G protein cycle and described not only the steric features of the Gα structure, but also conformational changes at each step. Each reference structure in the G protein cycle was modeled as an elastic network model and subjected to normal mode analysis. Our simulation data suggests that activated receptors trigger conformational changes of the Gα subunit that are thermodynamically favorable for opening of the nucleotide-binding pocket and GDP release. Furthermore, the effects of GTP binding and hydrolysis on mobility changes of the C and N termini and switch regions are elucidated. In summary, our simulation results enabled us to provide detailed descriptions of the structural and dynamic features of the G protein cycle. |
url |
http://europepmc.org/articles/PMC4970668?pdf=render |
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