To investigate the assembly of membrane proteins we use a combination of different theroetical and experimental techniques. In a series of numerical approaches we are using computer simulations and theoretical analysis to investigate the assembly process at various levels of detail (atomistic, coarse-grained and ultra-coarse grained). While at the experimental level we use spectroscopic, microscopic, molecular biology and synthetic biology methods to analyse the assembly process.
We have a series of biological systems that we investigate using these techniques: AqpZ, the Bacterial photosynthetic apparatus and mitochondrial anion channel, VDAC.
The membrane protein Aquaporin Z (AqpZ), from Escherichia coli forms a tetrameric water channel. However very little is known about the rules that govern membrane protein folding and assembly. We hope to be able to decode some of these rules by examining different steps in the folding of this protein.
Our research focusses on understanding the interactions between the protein and membrane lipids and in particular aspects of the protein surface and the lipid composition that modulate formation of tetrameric complexes and their subsequent assembly into 2D crystals. For this we are using various biochemical and biophysical techniques in the laboratory (fluorescence, FTIR spectroscopy, EM, lipidomics) or in collaboration with leading laboratories around the world (nmr, AFM and single molecule measurements).
A larger system we are studying is the bacterial photosynthetic system. This simple system forms specialized membranes composed essentially of 3 to 4 intergal membrane complexes. The different proteins are able to assemble spontaneously into specialise membranes within the bacteria, the morphology and composition of these domains are important for function, and we try to understand why certain proteins assemble into these domains and how their internal structure is determined.
Currently we are using multiple methods to modify the organization of membrane components, using molecular biology tools to modulate expression of the different components in living bacteria and constructing artificial photosynthetic systems bottom up. In both cases we study the organization and function of the system in order to elucidate the links between structure and function and the robustness of this simple integrated biological system.
The Voltage-Dependent Anion Channel (VDAC) is the most abundant protein in the OMM. Its three isoforms form β-barrel porins governing the flux of ions and metabolites between the organelle and the cytosol. Although VDAC’s transport function has been thoroughly studied, its role in mitochondrial regulation, as well as the function of eachisoform, remains elusive.
Numerous recent studies showed that interactions between pro-apoptotic Bax and Bak and VDAC are necessary to trigger cyt c release and the apoptosis cascade. Very limited data is available on the molecular mechanism of cyt c permeation. The characterization of the interaction between VDAC and Bax/Bak, and the complex(es) composition, formation or regulation are critical pieces missing to understand the molecular mechanism of this key event of apoptosis.
Our research focuses on identifying the exact composition, structure and regulation of VDAC and Bax/Bak pro-apoptotic complex(es). We use a combination of biochemical, biophysical (DEER, nMS, EM) and computational methods to investigate VDAC’s role in mitochondria-mediated apoptosis. This will expand our collective understanding of how these complexes assemble and trigger apoptosis, and establish hypothesis on the molecular mechanism behind cyt c release.
Yining Jiang, Batiste Thienpont, James Sturgis, Jeremy Dittman, Simon Scheuring
Biophysical Journal 121:433a (2022)10.1016/j.bpj.2021.11.608
Sinan Al-Attar, Julia Rendon, Marlon Sidore, Jean-Pierre Duneau, Farida Seduk, Frédéric Biaso, Stéphane Grimaldi, Bruno Guigliarelli, Axel Magalon
ACS Catalysis 11:14303-14318 (2021)10.1021/acscatal.1c03988
Ashley Tong, Olivia Fiebig, Muath Nairat, Dvir Harris, Marcel Giansily, Aurélia Chenu, James Sturgis, Gabriela Schlau-Cohen
Journal of Physical Chemistry B 124:1460-1469 (2020)10.1021/acs.jpcb.9b11899
Francesca Zuttion, Adai Colom, Stefan Matile, Denes Farago, Frédérique Pompeo, Janos Kokavecz, Anne Galinier, James Sturgis, Ignacio Casuso
Nature Communications 11 (2020)10.1038/s41467-020-19710-z
Mickaël Canestrari, Bastien Serrano, Julia Bartoli, Valerie Prima, Olivier Bornet, Rémy Puppo, Emmanuelle Bouveret, Francoise Guerlesquin, Julie Viala
FEBS Letters (2019)10.1002/1873-3468.13593
Victoria Schmidt, Marlon Sidore, Cherine Bechara, Jean-Pierre Duneau, James Sturgis
Biochimica et Biophysica Acta:Biomembranes 1861:431-440 (2019)10.1016/j.bbamem.2018.10.017
Ilaria Nardecchia, Jeremie Torres, Mathias Lechelon, Valeria Giliberti, Michele Ortolani, Philippe Nouvel, Matteo Gori, Yoann Meriguet, Irene Donato, Jordane Preto, Luca Varani, James Sturgis, Marco Pettini
Physical Review X 8:031061 (2018)10.1103/physrevx.8.031061
Victoria Schmidt, James Sturgis
Bio-protocol 8 (2018)10.21769/BioProtoc.2969
Victoria Schmidt, James Sturgis
Biochimica et Biophysica Acta:Biomembranes 1860:777-783 (2018)10.1016/j.bbamem.2017.12.012
Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre España, Laure Journet, Françoise Guerlesquin, E. Cascales
Journal of Molecular Biology 430:987-1003 (2018)10.1016/j.jmb.2018.02.008
Victoria Schmidt, James Sturgis
ACS Omega 2:3017-3027 (2017)10.1021/acsomega.7b00261
James Sturgis, Jean-Pierre Duneau, Jonathan Khao
Biochimica et Biophysica Acta:Biomembranes 1859:126-134 (2017)10.1016/j.bbamem.2016.10.014
Julie Viala, Valerie Prima, Remy Puppo, Rym Agrebi, Mickael J. Canestrari, Sabrina Lignon, Nicolas Chauvin, Stephane Meresse, Tam Mignot, Regine Lebrun, Emmanuelle Bouveret
PLoS Genetics 13 (2017)10.1371/journal.pgen.1006556
James Sturgis, Wang Dong
F1000Research 5 (2016)10.12688/f1000research.8676.1
Schmidt Victoria, Sidore Marlon, Carrière Fredéric, Duneau Jean-Pierre, James Sturgis
Biophysical Journal 110:252a-253a (2016)10.1016/j.bpj.2015.11.1389
Victoria Schmidt, Pierre Hubert, James Sturgis
Eur. Biophys. J. 44:S217 (2015)
Samia Aci-Sèche, Paul Sawma, Pierre Hubert, James Sturgis, Dominique Bagnard, Laurent Jacob, Monique Genest, Norbert Garnier
PLoS ONE 9:e97779 (2014)10.1371/journal.pone.0097779
Marco Ferretti, Katia Duquesne, James Sturgis, Rienk Grondelle
Physical Chemistry Chemical Physics 16:26059-66 (2014)10.1039/c4cp02986k
Paul Sawma, Lise Roth, Cécile Blanchard, Dominique Bagnard, Gérard Crémel, Emmanuelle Bouveret, Jean-Pierre Duneau, James Sturgis, Pierre Hubert
Journal of Molecular Biology 426:4099-111 (2014)10.1016/j.jmb.2014.10.007
Simon Scheuring, Reinat Nevo, Lu-Ning Liu, Stéphanie Mangenot, Dana Charuvi, Thomas Boudier, Valerie Prima, Pierre Hubert, James Sturgis, Ziv Reich
Biochimica biophysica acta (BBA) - Bioenergetics 1837:1263-1270 (2014)10.1016/j.bbabio.2014.03.011
Victoria Schmidt, Pierre Hubert, Valerie Prima, James Sturgis
Biophysical Journal 108:499a-500a (2014)
Gilles Breuzard, Pierre Hubert, Roqiya Nouar, Tiphany De Bessa, François Devred, Pascale Barbier, James Sturgis, Vincent Peyrot
Journal of Cell Science 126:2810-9 (2013)10.1242/jcs.120832
Jean-Pierre Duneau, James Sturgis
Eur. Biophys. J. 42:843-50 (2013)10.1007/s00249-013-0933-x
A Bernadac, L-F Wu, C-L Santini, C Vidaud, James Sturgis, N Menguy, P Bergam, C Nicoletti, T Xiao
Scientific Reports 2:950 (2012)10.1038/srep00950
Ignacio Casuso, Jean-Pierre Duneau, Mohamed Chami, Perrine Paul-Gilloteaux, Mohamed Husain, Jonathan Khao, Henning Stahlberg, James Sturgis, Simon Scheuring
Biophysical Journal 102:413a-414a (2012)10.1016/j.bpj.2011.11.2261
Ignacio Casuso, Jonathan Khao, Mohamed Chami, Perrine Paul-Gilloteaux, Mohamed Husain, Jean-Pierre Duneau, Henning Stahlberg, James Sturgis, Simon Scheuring
Nature Nanotechnology 525-529 (2012)10.1038/nnano.2012.109
K Duquesne, Valérie Prima, B Ji, Z Rouy, C Médigue, E Talla, James Sturgis
Journal of Bacteriology 194:3559-60 (2012)10.1128/JB.00605-12
K Duquesne, James Sturgis
Journal of Bacteriology 194:2380 (2012)10.1128/JB.00168-12
Katia Duquesne, Cecile Blanchard, James Sturgis
Biochemistry 50:6723-9 (2011)10.1021/bi200538j
Jonathan Khao, Jaime Arce-Lopera, James Sturgis, Jean-Pierre Duneau
Eur. Biophys. J. 40:1143-55 (2011)10.1007/s00249-011-0745-9
Lu-Ning Liu, James Sturgis, Simon Scheuring
Journal of Structural Biology 173:138-45 (2011)10.1016/j.jsb.2010.08.010
Astrid Wahl, Laetitia My, Romain Dumoulin, James Sturgis, Emmanuelle Bouveret
Mol. Microbiol. 80:1260-75 (2011)10.1111/j.1365-2958.2011.07641.x
Kamil Woronowicz, Daniel Sha, Raoul N Frese, James Sturgis, Vikas Nanda, Robert A Niederman
Metallomics 3:765-74 (2011)10.1039/c1mt00034a
Szymon Jarosławski, Katia Duquesne, James Sturgis, Simon Scheuring
Molecular Microbiology 74:1211-1222 (2009)10.1111/j.1365-2958.2009.06926.x
Nikolay Buzhynskyy, Pierre Sens, Valérie Prima, James Sturgis, Simon Scheuring
Biophysical Journal 93:2870-2876 (2007)10.1529/biophysj.107.109728
E. Etienne, P.-F. Lenne, James Sturgis, H. Rigneault
Applied optics 45:4497-4507 (2006)10.1364/AO.45.004497
Simon Scheuring, Rui Pedro Goncalves, Valérie Prima, James Sturgis
Journal of Molecular Biology in press:in press (2006)
E. Cascales, Roland Lloubès, James Sturgis
Molecular Microbiology 42:795-807 (2001)10.1046/j.1365-2958.2001.02673.x
E. Cascales, Marthe Gavioli, James Sturgis, Roland Lloubes
Molecular Microbiology 38:904-915 (2000)10.1046/j.1365-2958.2000.02190.x
Jean-Marie Peloponese, C. Gregoire, S Opi, E Esquieu, James Sturgis, E Lebrun, E. Meurs, C Collette, D Olive, M Aubertin, M Witvrow, C Pannecouque, E de Clercq, Cedric Bailly, J. Lebreton, E. Loret
Comptes rendus de l’Académie des sciences. Série III, Sciences de la vie 323:883-94 (2000)10.1016/S0764-4469(00)01228-2