PLD2-PI(4,5)P2 interactions in fluid phase membranes: Structural modeling and molecular dynamics simulations

PloS One
Kyungreem HanCristina Fenollar-Ferrer

Abstract

Interaction of phospholipase D2 (PLD2) with phosphatidylinositol (4,5)-bisphosphate (PIP2) is regarded as the critical step of numerous physiological processes. Here we build a full-length model of human PLD2 (hPLD2) combining template-based and ab initio modeling techniques and use microsecond all-atom molecular dynamics (MD) simulations of the protein in contact with a complex membrane to determine hPLD2-PIP2 interactions. MD simulations reveal that the intermolecular interactions preferentially occur between specific PIP2 phosphate groups and hPLD2 residues; the most strongly interacting residues are arginine at the pbox consensus sequence (PX) and pleckstrin homology (PH) domain. Interaction networks indicate formation of clusters at the protein-membrane interface consisting of amino acids, PIP2, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid (POPA); the largest cluster was in the PH domain.

References

Jan 1, 1985·International Review of Neurobiology·K W Miller
Feb 17, 1994·Nature·N P Franks, W R Lieb
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Jul 30, 1999·Biochimica Et Biophysica Acta·M A FrohmanA J Morris
May 4, 2002·Annual Review of Biophysics and Biomolecular Structure·Stuart McLaughlinDiana Murray
Jun 1, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Hércules Menezes, Carlos Jared
Dec 18, 2002·The Journal of Cell Biology·Vicki A SciorraAndrew J Morris
Jan 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tibor RohácsDiomedes E Logothetis
Apr 17, 2003·Molecular and Cellular Biology·Bong-Hyun AhnDo Sik Min
May 23, 2003·The New England Journal of Medicine·Jason A CampagnaStuart A Forman
Nov 25, 2003·Advances in Protein Chemistry·Jay W Ponder, David A Case
Dec 31, 2003·Methods in Enzymology·András Fiser, Andrej Sali
Aug 24, 2004·Nature Reviews. Neuroscience·Uwe Rudolph, Bernd Antkowiak
Dec 4, 2004·The EMBO Journal·Jean CheminEric Honoré
Jan 29, 2005·The Journal of Physiology·Coeli M B LopesDiomedes E Logothetis
Jul 27, 2005·Journal of Neurochemistry·Jochen Klein
Sep 7, 2005·Cellular and Molecular Life Sciences : CMLS·G M Jenkins, M A Frohman
Sep 28, 2005·The Journal of Biological Chemistry·Zheng ZhangEmily R Liman
Mar 22, 2007·Nature Reviews. Neuroscience·Eric Honoré
Mar 27, 2007·Pflügers Archiv : European journal of physiology·Jean CheminEric Honore
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
Apr 22, 2008·Nature Reviews. Neuroscience·Nicholas P Franks
Jun 25, 2008·Annual Review of Biophysics·Byung-Chang Suh, Bertil Hille
Jul 23, 2008·The Journal of Cell Biology·Declan J JamesThomas F J Martin
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Jul 25, 2009·Proteins·Andrea HildebrandJohannes Söding
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Sep 23, 2011·Chemical Reviews·Paige E SelvyH Alex Brown
Dec 27, 2011·Nature Methods·Michael RemmertJohannes Söding
Jul 25, 2012·Biophysical Journal·Y Zenmei OhkuboEmad Tajkhorshid
Sep 12, 2012·BMC Bioinformatics·Arjun RayBjörn Wallner
Dec 12, 2012·Journal of Computational Chemistry·Olga Yuzlenko, Themis Lazaridis
May 28, 2013·Chemical Society Reviews·Siewert J Marrink, D Peter Tieleman
Jul 9, 2013·Journal of Computational Chemistry·Jing Huang, Alexander D MacKerell
Sep 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hetunandan KamisettyDavid Baker
Jun 2, 2014·Nature Chemical Biology·Peter J HamiltonAurelio Galli
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yannick ComoglioGuillaume Sandoz

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Citations

Aug 10, 2021·Frontiers in Cell and Developmental Biology·Troy A KervinMichael Overduin

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Methods Mentioned

BETA
Two
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Software Mentioned

GREMLIN
HHpred
PROCHECK
VMD
ConSurf
MODELLER
CHARMM
PROPKA
- GUI
PLD2

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