James Sturgis’ research group is interested in the dynamics and assembly of membrane proteins. We are interested in how membrane proteins fold and assemble in the membrane to form both stable structures, such as the photosynthetic apparatus, or transient dynamic structures.

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.

1 – AqpZ assembly

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).

AFM image of AqpZ crystals disolving
in a lipid membrane (Coll. S. Scheuring).

2 – Organization of the bacterial photosynthetic apparatus

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.

3 – VDAC and Interactions

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.

Multidisciplinary approach to study VDAC complexes.
A. Hypothetical VDAC:Bax complex in nanodisc. Red dots are possible positions for DEER labeling. B. Typical DEER data. C. Negatively stained nanodiscs containing 1 or 2 VDAC channels. D. nMS spectrum of mVDAC1.

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.

Publications

2020
Comparison of the Energy-Transfer Rates in Structural and Spectral Variants of the B800–850 Complex from Purple Bacteria

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

2020
High-speed atomic force microscopy highlights new molecular mechanism of daptomycin action

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

2019
Deciphering the specific interaction between the acyl carrier protein IacP and the T3SS‐major hydrophobic translocator SipB from Salmonella

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

2019
The lipid environment of Escherichia coli Aquaporin Z

Victoria Schmidt, Marlon Sidore, Chérine Bechara, Jean-Pierre Duneau, James Sturgis

Biochimica et Biophysica Acta:Biomembranes 1861:431-440 (2019)10.1016/j.bbamem.2018.10.017

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2018
Out-of-Equilibrium Collective Oscillation as Phonon Condensation in a Model Protein

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

2018
Modifying styrene-maleic acid co-polymer for studying lipid nanodiscs

Victoria Schmidt, James Sturgis

Biochimica et Biophysica Acta:Biomembranes 1860:777-783 (2018)10.1016/j.bbamem.2017.12.012

2018
Tryptophan-mediated Dimerization of the TssL Transmembrane Anchor Is Required for Type VI Secretion System Activity

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

2017
Lipid perturbation by membrane proteins and the lipophobic effect

James Sturgis, Jean-Pierre Duneau, Jonathan Khao

Biochimica et Biophysica Acta:Biomembranes 1859:126-134 (2017)10.1016/j.bbamem.2016.10.014

2017
Acylation of the Type 3 Secretion System Translocon Using a Dedicated Acyl Carrier Protein

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

2016
Lipid Environment of Aquaporin Z

Schmidt Victoria, Sidore Marlon, Carrière Fredéric, Duneau Jean-Pierre, James Sturgis

Biophysical Journal 110:252a-253a (2016)10.1016/j.bpj.2015.11.1389

2015
The E.coli Aquaporin Z interface : a puzzle?

Victoria Schmidt, Pierre Hubert, James Sturgis

Eur. Biophys. J. 44:S217 (2015)

2014
Transmembrane Recognition of the Semaphorin Co-Receptors Neuropilin 1 and Plexin A1 : Coarse-Grained Simulations

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

2014
Ultrafast excited state processes in Roseobacter denitrificans antennae: comparison of isolated complexes and native membranes.

Marco Ferretti, Katia Duquesne, James Sturgis, Rienk Grondelle

Physical Chemistry Chemical Physics 16:26059-66 (2014)10.1039/c4cp02986k

2014
Evidence for new homotypic and heterotypic interactions between transmembrane helices of proteins involved in receptor tyrosine kinase and neuropilin signaling.

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

2014
The architecture of Rhodobacter sphaeroides chromatophores

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

2014
Destabilizing Aquaporin Z Assembly: Effects on Structure, Function and Dynamics

Victoria Schmidt, Pierre Hubert, Valerie Prima, James Sturgis

Biophysical Journal 108:499a-500a (2014)

2013
Molecular mechanisms of Tau binding to microtubules and its role in microtubule dynamics in live cells.

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

2013
2012
Structural properties of the tubular appendage spinae from marine bacterium Roseobacter sp. strain YSCB.

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

2012
Complete Lateral and Angular Diffusion and Protein-Protein Interaction Description of a Membrane Protein

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

2012
Characterization of the motion of membrane proteins using high-speed atomic force microscopy

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

2012
Draft genome sequence of the purple photosynthetic bacterium Phaeospirillum molischianum DSM120, a particularly versatile bacterium.

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

2011
Molecular origins and consequences of High-800 LH2 in Roseobacter denitrificans.

Katia Duquesne, Cecile Blanchard, James Sturgis

Biochemistry 50:6723-9 (2011)10.1021/bi200538j

2011
Structure of a protein-detergent complex: the balance between detergent cohesion and binding.

Jonathan Khao, Jaime Arce-Lopera, James Sturgis, Jean-Pierre Duneau

Eur. Biophys. J. 40:1143-55 (2011)10.1007/s00249-011-0745-9

2011
Native architecture of the photosynthetic membrane from Rhodobacter veldkampii.

Lu-Ning Liu, James Sturgis, Simon Scheuring

Journal of Structural Biology 173:138-45 (2011)10.1016/j.jsb.2010.08.010

2011
Antagonistic regulation of dgkA and plsB genes of phospholipid synthesis by multiple stress responses in Escherichia coli.

Astrid Wahl, Laetitia My, Romain Dumoulin, James Sturgis, Emmanuelle Bouveret

Mol. Microbiol. 80:1260-75 (2011)10.1111/j.1365-2958.2011.07641.x

2009
High-resolution architecture of the outer membrane of the Gram-negative bacteria Roseobacter denitrificans.

Szymon Jarosławski, Katia Duquesne, James Sturgis, Simon Scheuring

Molecular Microbiology 74:1211-1222 (2009)10.1111/j.1365-2958.2009.06926.x

2007
Rows of ATP Synthase Dimers in Native Mitochondrial Inner Membranes

Nikolay Buzhynskyy, Pierre Sens, Valérie Prima, James Sturgis, Simon Scheuring

Biophysical Journal 93:2870-2876 (2007)10.1529/biophysj.107.109728

2006
Confined diffusion in tubular structures analyzed by fluorescence correlation spectroscopy on a mirror

E. Etienne, P.-F. Lenne, James Sturgis, H. Rigneault

Applied optics 45:4497-4507 (2006)10.1364/AO.45.004497

2006
The photosynthetic apparatus of Rhodopseudomonas palustris: Structures and organization.

Simon Scheuring, Rui Pedro Goncalves, Valérie Prima, James Sturgis

Journal of Molecular Biology in press:in press (2006)

2001
2000
2000
1H-13C nuclear magnetic resonance assignment and structural characterization of HIV-1 Tat protein.

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

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Collaborations

  • National
    • Olivia du Roure, ESPCI ParisTech
    • Julien Heuvingh, ESPCI ParisTech
    • Clément Campillo, Université d’Evry
    • Guido Pintacuda, CNRS ISA, Lyon
    • Marco Pettini, CNRS CPT, Marseille
    • Ignacio Casuso, INSERM, Marseille
  • International
    • David Kovar University of Chicago, USA
    • Robert Robinson IMCB, Singapore
    • Simon Scheuring, Corning Medical School, USA
    • Janice Robertson, Washington University, USA
    • Gabriela Schlau-Cohen, MIT, USA
    • Alexandra Olaya-Castro, UCL, UK
    • Luca Sapienza, Southampton University, UK

Funding

© 2021 LISM - Laboratoire d'Ingénierie des Systèmes Macromoléculaires - CNRS UMR7255

31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France