Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis

Scientific Reports
Manuel P LuitzMartin Zacharias

Abstract

The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G G PrivéS H Kim
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Apr 2, 2003·Biochemistry·Robert A PhillipsMartin R Webb
May 22, 2003·Journal of Computational Chemistry·Kristin L MeagherHeather A Carlson
Jun 6, 2003·Biochemical and Biophysical Research Communications·Thomas WeideAngelika Barnekow
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Feb 8, 2005·Biochemical and Biophysical Research Communications·Julia FischerAngelika Barnekow
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
May 4, 2007·Experimental Cell Research·Mechthild RosingAngelika Barnekow
Oct 24, 2007·Nature·Alyssa IngmundsonCraig R Roy
Apr 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Carsten KöttingKlaus Gerwert
Apr 14, 2009·Molecular Cell·Carolyn A WorbyJack E Dixon
Nov 13, 2009·Optics Express·Gavin D M JeffriesDaniel T Chiu
Apr 22, 2010·Proteins·Kresten Lindorff-LarsenDavid E Shaw
Jun 1, 2010·Nature Chemical Biology·Yao-Wen WuRoger S Goody
Jun 17, 2011·Nature Reviews. Microbiology·Klaus Aktories
Sep 16, 2011·Angewandte Chemie·Cornelis SmitChristian Hedberg
Jul 25, 2012·BMC Research Notes·Alan W Sousa da Silva, Wim F Vranken
Aug 9, 2012·The Journal of Biological Chemistry·Matthias P MüllerAymelt Itzen
Jan 11, 2013·Physiological Reviews·Jacqueline Cherfils, Mahel Zeghouf
Mar 13, 2015·The Journal of Physical Chemistry. B·Stefano PianaDavid E Shaw
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl

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Citations

Oct 2, 2019·Frontiers in Cell and Developmental Biology·Peter M Luo, Michael Boyce
Apr 13, 2018·International Journal of Molecular Sciences·Miriam SchöpelRaphael Stoll
Mar 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Katja BarthelmesAymelt Itzen
Jan 21, 2021·Nature Communications·Jiqing DuAymelt Itzen
Aug 19, 2017·Chemical Reviews·Amanda K Casey, Kim Orth

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Methods Mentioned

BETA
GTPases
GTPase
X-ray
nuclear magnetic resonance
glycosylation
gel filtration
size exclusion chromatography

Software Mentioned

APBS
Gaussian03
AmberTools13
Gromacs
GAFF
OriginPro
LINear Constraint Solver
acype
cluster
antechamber

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