Versatile Dimerisation Process of Translocator Protein (TSPO) Revealed by an Extensive Sampling Based on a Coarse-Grained Dynamics Study.

Journal of Chemical Information and Modeling
Rajas RaoCatherine Etchebest

Abstract

Translocator protein (TSPO), a mitochondrial membrane protein, has been extensively studied, and its role is still debated and continues to be enigmatic. From a structural perspective, despite availability of atomic structures from different species, the possible oligomeric state and its 3D structure remains elusive. In the present study, we attempted to study dynamics of TSPO from the perspective of oligomerization. In this aim, we examined if and how TSPO monomers could assemble to form a dimer. Accordingly, we performed several coarse-grained molecular dynamics simulations considering two different initial configurations, one with a pair of TSPO monomers distantly placed in a model of a bilayer composed of DMPC/cholesterol mixture and the other with preformed dimer models with different starting interactions. We identify stable TSPO dimers with diverse interfaces, some of which were consistent with earlier experimental observations on putative TSPO oligomer interfaces. For most of the stable ones, interactions between aromatic residues were significantly overrepresented in diverse oligomeric organizations. Interestingly, we identified different communication pathways that involve dimer interfaces. Additionally, we observed t...Continue Reading

References

Sep 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·C Braestrup, R F Squires
Dec 29, 1992·Biochemistry·M A LemmonD M Engelman
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A G MukhinK E Krueger
Mar 24, 1995·European Journal of Pharmacology·L D McCauleyK W Gee
Aug 1, 1994·Molecular and Cellular Endocrinology·V PapadopoulosB Vidic
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·F X ZhouD M Engelman
Jun 8, 2001·Biochemical and Biophysical Research Communications·J J LacapèreB Vidic
Apr 20, 2002·Biophysical Journal·Markus EilersSteven O Smith
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Nov 11, 2005·Journal of Molecular Biology·Anja RidderDieter Langosch
Aug 31, 2006·Bioinformatics·Barry J GrantLeo S D Caves
Jan 27, 2007·Biochemistry·Jean-Pierre DuneauJames N Sturgis
Feb 7, 2007·Molecular and Cellular Endocrinology·Vassilios PapadopoulosMartine Culty
Jun 16, 2007·The Journal of Physical Chemistry. B·Siewert J MarrinkAlex H de Vries
Oct 24, 2007·Journal of Molecular Biology·Stephanie UnterreitmeierDieter Langosch
Aug 2, 2008·Journal of Bioenergetics and Biomembranes·Leo VeenmanMoshe Gavish
Sep 16, 2008·Cellular Oncology : the Official Journal of the International Society for Cellular Oncology·Wilfried KuglerMoshe Gavish
May 7, 2009·Biochemistry·Endah S Sulistijo, Kevin R Mackenzie
Sep 3, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christine RamponSophie Vriz
Sep 5, 2009·The Journal of Biological Chemistry·Jinjiang FanVassilios Papadopoulos
Jun 15, 2010·Structure·Vladimir M KorkhovChristopher G Tate
Jun 16, 2010·PLoS Computational Biology·Semen O YesylevskyySiewert J Marrink
Mar 29, 2011·Journal of Chemical Information and Modeling·Andrei L LomizeHenry I Mosberg
Sep 6, 2011·Nucleic Acids Research·Mikhail A LomizeAndrei L Lomize
Sep 14, 2011·Biochimica Et Biophysica Acta·Edwin LiKalina Hristova
May 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Denys PogoryelovThomas Meier
Feb 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Benjamin K MuellerAlessandro Senes
May 13, 2014·Protein Science : a Publication of the Protein Society·Lukasz JaremkoMarkus Zweckstetter
Oct 28, 2014·Brain Pathology·Guo-Jun LiuRichard B Banati
Jan 31, 2015·Science·Youzhong GuoWayne A Hendrickson
Mar 25, 2015·Trends in Endocrinology and Metabolism : TEM·Vimal Selvaraj, Douglas M Stocco
Sep 28, 2015·Journal of Molecular Biology·G C P van ZundertA M J J Bonvin
Nov 10, 2015·Biochemical Society Transactions·Mariusz JaremkoMarkus Zweckstetter
Feb 11, 2014·Journal of Chemical Theory and Computation·Tsjerk A WassenaarD Peter Tieleman
Jan 8, 2013·Journal of Chemical Theory and Computation·Djurre H de JongSiewert J Marrink

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Citations

Sep 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zeineb Si ChaibGiulia Rossetti
Mar 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hien T T LaiAgata Kranjc

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