English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Role of structural dynamics at the receptor G protein interface for signal transduction.

Rose, A. S., Zachariae, U., Grubmüller, H., Hofmann, K. P., Scheerer, P., & Hildebrand, W. (2015). Role of structural dynamics at the receptor G protein interface for signal transduction. PLOS One, 10(11): e0143399. doi:10.1371/journal.pone.0143399.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-4471-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6EEE-D
Genre: Journal Article

Files

show Files
hide Files
:
2240338.pdf (Publisher version), 2MB
Name:
2240338.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
:
2240338_Suppl.PDF (Supplementary material), 8MB
Name:
2240338_Suppl.PDF
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Rose, A. S., Author
Zachariae, U.1, Author              
Grubmüller, H.2, Author              
Hofmann, K. P., Author
Scheerer, P., Author
Hildebrand, W., Author
Affiliations:
1Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578573              
2Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society, ou_578631              

Content

show
hide
Free keywords: -
 Abstract: GPCRs catalyze GDP/GTP exchange in the a-subunit of heterotrimeric G proteins (G alpha beta gamma) through displacement of the G alpha C-terminal alpha 5 helix, which directly connects the interface of the active receptor (R*) to the nucleotide binding pocket of G. Hydrogen-deuterium exchange mass spectrometry and kinetic analysis of R* catalysed G protein activation have suggested that displacement of a5 starts from an intermediate GDP bound complex (R*center dot G(GDP)). To elucidate the structural basis of receptor-catalysed displacement of alpha 5, we modelled the structure of R*center dot G(GDP). A flexible docking protocol yielded an intermediate R*center dot G(GDP) complex, with a similar overall arrangement as in the X-ray structure of the nucleotide free complex (R*center dot G(empty)), however with the alpha 5 C-terminus (G alpha CT) forming different polar contacts with R*. Starting molecular dynamics simulations of G alpha CT bound to R* in the intermediate position, we observe a screw-like motion, which restores the specific interactions of alpha 5 with R* in R*center dot G(empty). The observed rotation of alpha 5 by 60 degrees is in line with experimental data. Reformation of hydrogen bonds, water expulsion and formation of hydrophobic interactions are driving forces of the alpha 5 displacement. We conclude that the identified interactions between R* and G protein define a structural framework in which the alpha 5 displacement promotes direct transmission of the signal from R* to the GDP binding pocket.

Details

show
hide
Language(s): eng - English
 Dates: 2015-11-25
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pone.0143399
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLOS One
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 13 Volume / Issue: 10 (11) Sequence Number: e0143399 Start / End Page: - Identifier: -