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.
Olivia Fiebig, Dihao Wang, Dvir Harris, Hila Toporik, Yi Ji, Chern Chuang, Muath Nairat, Ashley Tong, John Ogren, Stephanie Hart, Jianshu Cao, James N. Sturgis, Yuval Mazor, Gabriela Schlau-Cohen
Biophysical Journal 122:232a (2023)10.1016/j.bpj.2022.11.1368
Dihao Wang, Olivia Fiebig, Dvir Harris, Hila Toporik, Yi Ji, Chern Chuang, Muath Nairat, Ashley Tong, John Ogren, Stephanie Hart, Jianshu Cao, James Sturgis, Yuval Mazor, Gabriela Schlau-Cohen
Proceedings of the National Academy of Sciences of the United States of America 120:e2220477120 (2023)10.1073/pnas.2220477120
Yining Jiang, Batiste Thienpont, James N. Sturgis, Jeremy Dittman, Simon Scheuring
Biophysical Journal 121:433a (2022)10.1016/j.bpj.2021.11.608
Yining Jiang, Batiste Thienpont, Vinay Sapuru, Richard Hite, Jeremy Dittman, James Sturgis, Simon Scheuring
Nature Communications 13:7373 (2022)10.1038/s41467-022-35202-8
Mathias Lechelon, Yoann Meriguet, Matteo Gori, Sandra Ruffenach, Ilaria Nardecchia, Elena Floriani, Dominique Coquillat, Frederic Teppe, Sébastien Mailfert, Didier Marguet, Pierre Ferrier, Luca Varani, James Sturgis, Jeremie Torres, Pettini Marco
Science Advances 8:eabl5855 (2022)10.1126/sciadv.abl5855
Van A. Ngo, María Queralt-Martín, Farha Khan, Lucie Bergdoll, Jeff Abramson, Sergey m. Bezrukov, Tatiana K Rostovtseva, David P Hoogerheide, Sergei Yu Noskov
Journal of the American Chemical Society 144:14564-14577 (2022)10.1021/jacs.2c03316
Ashley Tong, Olivia Fiebig, Muath Nairat, Dvir Harris, Marcel Giansily, Aurélia Chenu, James N. 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 N. Sturgis, Ignacio Casuso
Nature Communications 11 (2020)10.1038/s41467-020-19710-z
Victoria Schmidt, Marlon Sidore, Cherine Bechara, Jean-Pierre Duneau, James N. 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 N. Sturgis, Marco Pettini
Physical Review X 8:031061 (2018)10.1103/physrevx.8.031061
Victoria Schmidt, James N. Sturgis
Bio-protocol 8 (2018)10.21769/BioProtoc.2969
Victoria Schmidt, James N. Sturgis
Biochimica et Biophysica Acta:Biomembranes 1860:777-783 (2018)10.1016/j.bbamem.2017.12.012
Victoria Schmidt, James N. Sturgis
ACS Omega 2:3017-3027 (2017)10.1021/acsomega.7b00261
James N. Sturgis, Jean-Pierre Duneau, Jonathan Khao
Biochimica et Biophysica Acta:Biomembranes 1859:126-134 (2017)10.1016/j.bbamem.2016.10.014
James N. Sturgis, Wang Dong
F1000Research 5 (2016)10.12688/f1000research.8676.1
Schmidt Victoria, Sidore Marlon, Carrière Fredéric, Duneau Jean-Pierre, James N. Sturgis
Biophysical Journal 110:252a-253a (2016)10.1016/j.bpj.2015.11.1389
Victoria Schmidt, Pierre Hubert, James N. Sturgis
Eur. Biophys. J. 44:S217 (2015)
Samia Aci-Sèche, Paul Sawma, Pierre Hubert, James N. Sturgis, Dominique Bagnard, Laurent Jacob, Monique Genest, Norbert Garnier
PLoS ONE 9:e97779 (2014)10.1371/journal.pone.0097779
Marco Ferretti, Katia Duquesne, James N. Sturgis, Rienk Van 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 N. 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 N. 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 N. Sturgis
Biophysical Journal 108:499a-500a (2014)
Gilles Breuzard, Pierre Hubert, Roqiya Nouar, Tiphany De Bessa, François Devred, Pascale Barbier, James N. Sturgis, Vincent Peyrot
Journal of Cell Science 126:2810-9 (2013)10.1242/jcs.120832
Jean-Pierre Duneau, James N. 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 N. Sturgis, N Menguy, P Bergam, C Nicoletti, T Xiao
Scientific Reports 2:950 (2012)10.1038/srep00950
Ignacio Casuso, Jonathan Khao, Mohamed Chami, Perrine Paul-Gilloteaux, Mohamed Husain, Jean-Pierre Duneau, Henning Stahlberg, James N. Sturgis, Simon Scheuring
Nature Nanotechnology 525-529 (2012)10.1038/nnano.2012.109
Ignacio Casuso, Jean-Pierre Duneau, Mohamed Chami, Perrine Paul-Gilloteaux, Mohamed Husain, Jonathan Khao, Henning Stahlberg, James N. Sturgis, Simon Scheuring
Biophysical Journal 102:413a-414a (2012)10.1016/j.bpj.2011.11.2261
K Duquesne, Valérie Prima, B Ji, Z Rouy, C Médigue, E Talla, James N. Sturgis
Journal of Bacteriology 194:3559-60 (2012)10.1128/JB.00605-12
K Duquesne, James N. Sturgis
Journal of Bacteriology 194:2380 (2012)10.1128/JB.00168-12
Katia Duquesne, Cecile Blanchard, James N. Sturgis
Biochemistry 50:6723-9 (2011)10.1021/bi200538j
Jonathan Khao, Jaime Arce-Lopera, James N. Sturgis, Jean-Pierre Duneau
Eur. Biophys. J. 40:1143-55 (2011)10.1007/s00249-011-0745-9
Lu-Ning Liu, James N. Sturgis, Simon Scheuring
Journal of Structural Biology 173:138-45 (2011)10.1016/j.jsb.2010.08.010
Astrid Wahl, Laetitia My, Romain R. Dumoulin, James N. 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 N. Sturgis, Vikas Nanda, Robert A Niederman
Metallomics 3:765-74 (2011)10.1039/c1mt00034a
Szymon Jarosławski, Katia Duquesne, James N. Sturgis, Simon Scheuring
Molecular Microbiology 74:1211-1222 (2009)10.1111/j.1365-2958.2009.06926.x
Nikolay Buzhynskyy, Pierre Sens, Valérie Prima, James N. Sturgis, Simon Scheuring
Biophysical Journal 93:2870-2876 (2007)10.1529/biophysj.107.109728
E. Etienne, P.-F. Lenne, James N. Sturgis, H. Rigneault
Applied optics 45:4497-4507 (2006)10.1364/AO.45.004497
Simon Scheuring, Rui Pedro Goncalves, Valérie Prima, James N. Sturgis
Journal of Molecular Biology in press:in press (2006)
E. Cascales, Roland Lloubès, James N. Sturgis
Molecular Microbiology 42:795-807 (2001)10.1046/j.1365-2958.2001.02673.x
E. Cascales, Marthe Gavioli, James N. 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 N. 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