How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins
Abstract
The spatiotemporal organisation of membranes is often characterised by the formation of large protein clusters. In Escherichia coli, outer membrane protein (OMP) clustering leads to OMP islands, the formation of which underpins OMP turnover and drives organisation across the cell envelope. Modelling how OMP islands form in order to understand their origin and outer membrane behaviour has been confounded by the inherent difficulties of simulating large numbers of OMPs over meaningful timescales. Here, we overcome these problems by training a mesoscale model incorporating thousands of OMPs on coarse-grained molecular dynamics simulations. We achieve simulations over timescales that allow direct comparison to experimental data of OMP behaviour. Here, we show that specific interaction surfaces between OMPs are key to the formation of OMP clusters, that OMP clusters present a mesh of moving barriers that confine newly inserted proteins within islands, and that mesoscale simulations recapitulate the restricted diffusion characteristics of OMPs.
- Authors:
-
- Univ. of Oxford (United Kingdom); Univ. de Toulouse, Toulouse (France)
- Univ. of Oxford (United Kingdom)
- Univ. of Oxford (United Kingdom); Univ. de Strasbourg, Illkirch (France)
- Univ. of Osnabrück, Osnabrück (Germany)
- Univ. of Oxford (United Kingdom); SEMMLE, Oxford (United Kingdom)
- Univ. of Oxford (United Kingdom); Radcliffe Observatory Quarter (550), Oxford (United Kingdom)
- Radcliffe Observatory Quarter (550), Oxford (United Kingdom)
- Univ. of Osnabrück, Barbarastraße (Osnabrück)
- Publication Date:
- Research Org.:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1570630
- Report Number(s):
- LA-UR-19-29545
Journal ID: ISSN 2041-1723
- Grant/Contract Number:
- 89233218CNA000001
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Chavent, Matthieu, Duncan, Anna L., Rassam, Patrice, Birkholz, Oliver, Hélie, Jean, Reddy, Tyler John Edward, Beliaev, Dmitry, Hambly, Ben, Piehler, Jacob, Kleanthous, Colin, and Sansom, Mark S. P. How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. United States: N. p., 2018.
Web. doi:10.1038/s41467-018-05255-9.
Chavent, Matthieu, Duncan, Anna L., Rassam, Patrice, Birkholz, Oliver, Hélie, Jean, Reddy, Tyler John Edward, Beliaev, Dmitry, Hambly, Ben, Piehler, Jacob, Kleanthous, Colin, & Sansom, Mark S. P. How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. United States. https://doi.org/10.1038/s41467-018-05255-9
Chavent, Matthieu, Duncan, Anna L., Rassam, Patrice, Birkholz, Oliver, Hélie, Jean, Reddy, Tyler John Edward, Beliaev, Dmitry, Hambly, Ben, Piehler, Jacob, Kleanthous, Colin, and Sansom, Mark S. P. Fri .
"How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins". United States. https://doi.org/10.1038/s41467-018-05255-9. https://www.osti.gov/servlets/purl/1570630.
@article{osti_1570630,
title = {How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins},
author = {Chavent, Matthieu and Duncan, Anna L. and Rassam, Patrice and Birkholz, Oliver and Hélie, Jean and Reddy, Tyler John Edward and Beliaev, Dmitry and Hambly, Ben and Piehler, Jacob and Kleanthous, Colin and Sansom, Mark S. P.},
abstractNote = {The spatiotemporal organisation of membranes is often characterised by the formation of large protein clusters. In Escherichia coli, outer membrane protein (OMP) clustering leads to OMP islands, the formation of which underpins OMP turnover and drives organisation across the cell envelope. Modelling how OMP islands form in order to understand their origin and outer membrane behaviour has been confounded by the inherent difficulties of simulating large numbers of OMPs over meaningful timescales. Here, we overcome these problems by training a mesoscale model incorporating thousands of OMPs on coarse-grained molecular dynamics simulations. We achieve simulations over timescales that allow direct comparison to experimental data of OMP behaviour. Here, we show that specific interaction surfaces between OMPs are key to the formation of OMP clusters, that OMP clusters present a mesh of moving barriers that confine newly inserted proteins within islands, and that mesoscale simulations recapitulate the restricted diffusion characteristics of OMPs.},
doi = {10.1038/s41467-018-05255-9},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {Fri Jul 20 00:00:00 EDT 2018},
month = {Fri Jul 20 00:00:00 EDT 2018}
}
Web of Science
Figures / Tables:
Works referenced in this record:
Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane
journal, April 2016
- Fujiwara, Takahiro K.; Iwasawa, Kokoro; Kalay, Ziya
- Molecular Biology of the Cell, Vol. 27, Issue 7
Membrane Proteins Diffuse as Dynamic Complexes with Lipids
journal, June 2010
- Niemelä, Perttu S.; Miettinen, Markus S.; Monticelli, Luca
- Journal of the American Chemical Society, Vol. 132, Issue 22
Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity
journal, April 2017
- Bergmiller, Tobias; Andersson, Anna M. C.; Tomasek, Kathrin
- Science, Vol. 356, Issue 6335
Intermembrane crosstalk drives inner-membrane protein organization in Escherichia coli
journal, March 2018
- Rassam, Patrice; Long, Kathleen R.; Kaminska, Renata
- Nature Communications, Vol. 9, Issue 1
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation
journal, February 2008
- Hess, Berk; Kutzner, Carsten; van der Spoel, David
- Journal of Chemical Theory and Computation, Vol. 4, Issue 3
The MARTINI Coarse-Grained Force Field: Extension to Proteins
journal, April 2008
- Monticelli, Luca; Kandasamy, Senthil K.; Periole, Xavier
- Journal of Chemical Theory and Computation, Vol. 4, Issue 5
Lipopolysaccharide Endotoxins
journal, June 2002
- Raetz, Christian R. H.; Whitfield, Chris
- Annual Review of Biochemistry, Vol. 71, Issue 1
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
journal, December 2003
- Nikaido, H.
- Microbiology and Molecular Biology Reviews, Vol. 67, Issue 4
Reconstitution of Membrane Proteins into Polymer-Supported Membranes for Probing Diffusion and Interactions by Single Molecule Techniques
journal, September 2011
- Roder, Friedrich; Waichman, Sharon; Paterok, Dirk
- Analytical Chemistry, Vol. 83, Issue 17
Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations
journal, October 2016
- Hedger, George; Sansom, Mark S. P.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1858, Issue 10
Analysis of Surface Protein Expression Reveals the Growth Pattern of the Gram-Negative Outer Membrane
journal, September 2012
- Ursell, Tristan S.; Trepagnier, Eliane H.; Huang, Kerwyn Casey
- PLoS Computational Biology, Vol. 8, Issue 9
Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale
journal, October 2016
- Chavent, Matthieu; Duncan, Anna L.; Sansom, Mark SP
- Current Opinion in Structural Biology, Vol. 40
Electrostatic rate enhancement and transient complex of protein–protein association
journal, January 2008
- Alsallaq, Ramzi; Zhou, Huan-Xiang
- Proteins: Structure, Function, and Bioinformatics, Vol. 71, Issue 1
Role of the Native Outer-Membrane Environment on the Transporter BtuB
journal, October 2016
- Balusek, Curtis; Gumbart, James C.
- Biophysical Journal, Vol. 111, Issue 7
NIH Image to ImageJ: 25 years of image analysis
journal, June 2012
- Schneider, Caroline A.; Rasband, Wayne S.; Eliceiri, Kevin W.
- Nature Methods, Vol. 9, Issue 7
The Free Energy Landscape of Dimerization of a Membrane Protein, NanC
journal, January 2014
- Dunton, Thomas A.; Goose, Joseph E.; Gavaghan, David J.
- PLoS Computational Biology, Vol. 10, Issue 1
Hierarchical mesoscale domain organization of the plasma membrane
journal, November 2011
- Kusumi, Akihiro; Suzuki, Kenichi G. N.; Kasai, Rinshi S.
- Trends in Biochemical Sciences, Vol. 36, Issue 11
A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli
journal, December 2015
- Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio
- Journal of Biological Chemistry, Vol. 291, Issue 4
Perspective on the Martini model
journal, January 2013
- Marrink, Siewert J.; Tieleman, D. Peter
- Chemical Society Reviews, Vol. 42, Issue 16
Structural basis of outer membrane protein insertion by the BAM complex
journal, February 2016
- Gu, Yinghong; Li, Huanyu; Dong, Haohao
- Nature, Vol. 531, Issue 7592
Receptor dimerization dynamics as a regulatory valve for plasticity of type I interferon signaling
journal, May 2015
- Wilmes, Stephan; Beutel, Oliver; Li, Zhi
- The Journal of Cell Biology, Vol. 209, Issue 4
Manipulation and Motion of Organelles and Single Molecules in Living Cells
journal, February 2017
- Norregaard, Kamilla; Metzler, Ralf; Ritter, Christine M.
- Chemical Reviews, Vol. 117, Issue 5
Molecular dynamics with coupling to an external bath
journal, October 1984
- Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.
- The Journal of Chemical Physics, Vol. 81, Issue 8
Combining an Elastic Network With a Coarse-Grained Molecular Force Field: Structure, Dynamics, and Intermolecular Recognition
journal, August 2009
- Periole, Xavier; Cavalli, Marco; Marrink, Siewert-Jan
- Journal of Chemical Theory and Computation, Vol. 5, Issue 9
A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins
journal, June 2000
- D. Ferguson, Andrew; Welte, Wolfram; Hofmann, Eckhard
- Structure, Vol. 8, Issue 6
g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation
journal, March 2010
- Wolf, Maarten G.; Hoefling, Martin; Aponte-Santamaría, Camilo
- Journal of Computational Chemistry, Vol. 31, Issue 11
Anomalous and normal diffusion of proteins and lipids in crowded lipid membranes
journal, January 2013
- Javanainen, Matti; Hammaren, Henrik; Monticelli, Luca
- Faraday Discuss., Vol. 161
Protein–protein interactions and the spatiotemporal dynamics of bacterial outer membrane proteins
journal, December 2015
- Kleanthous, Colin; Rassam, Patrice; Baumann, Christoph G.
- Current Opinion in Structural Biology, Vol. 35
Dynamical motions of lipids and a finite size effect in simulations of bilayers
journal, October 2006
- Klauda, Jeffery B.; Brooks, Bernard R.; Pastor, Richard W.
- The Journal of Chemical Physics, Vol. 125, Issue 14
Divergent Diffusion Coefficients in Simulations of Fluids and Lipid Membranes
journal, May 2016
- Vögele, Martin; Hummer, Gerhard
- The Journal of Physical Chemistry B, Vol. 120, Issue 33
Matplotlib: A 2D Graphics Environment
journal, January 2007
- Hunter, John D.
- Computing in Science & Engineering, Vol. 9, Issue 3
The NumPy Array: A Structure for Efficient Numerical Computation
journal, March 2011
- van der Walt, Stéfan; Colbert, S. Chris; Varoquaux, Gaël
- Computing in Science & Engineering, Vol. 13, Issue 2
Lipid Clustering Correlates with Membrane Curvature as Revealed by Molecular Simulations of Complex Lipid Bilayers
journal, October 2014
- Koldsø, Heidi; Shorthouse, David; Hélie, Jean
- PLoS Computational Biology, Vol. 10, Issue 10
VMD: Visual molecular dynamics
journal, February 1996
- Humphrey, William; Dalke, Andrew; Schulten, Klaus
- Journal of Molecular Graphics, Vol. 14, Issue 1
Protein area occupancy at the center of the red blood cell membrane
journal, February 2008
- Dupuy, A. D.; Engelman, D. M.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 8
Supramolecular Assembly of VDAC in Native Mitochondrial Outer Membranes
journal, June 2007
- Gonçalves, Rui Pedro; Buzhynskyy, Nikolay; Prima, Valérie
- Journal of Molecular Biology, Vol. 369, Issue 2
Modeling of loops in protein structures
journal, January 2000
- Fiser, András; Do, Richard Kinh Gian; Šali, Andrej
- Protein Science, Vol. 9, Issue 9
Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria
journal, June 2015
- Rassam, Patrice; Copeland, Nikki A.; Birkholz, Oliver
- Nature, Vol. 523, Issue 7560
Glasslike Membrane Protein Diffusion in a Crowded Membrane
journal, January 2016
- Munguira, Ignacio; Casuso, Ignacio; Takahashi, Hirohide
- ACS Nano, Vol. 10, Issue 2
Organization and Dynamics of Receptor Proteins in a Plasma Membrane
journal, November 2015
- Koldsø, Heidi; Sansom, Mark S. P.
- Journal of the American Chemical Society, Vol. 137, Issue 46
Quantifying Absolute Protein Synthesis Rates Reveals Principles Underlying Allocation of Cellular Resources
journal, April 2014
- Li, Gene-Wei; Burkhardt, David; Gross, Carol
- Cell, Vol. 157, Issue 3
Membrane protein sequestering by ionic protein–lipid interactions
journal, October 2011
- van den Bogaart, Geert; Meyenberg, Karsten; Risselada, H. Jelger
- Nature, Vol. 479, Issue 7374
It Is Complicated: Curvature, Diffusion, and Lipid Sorting within the Two Membranes of Escherichia coli
journal, October 2017
- Hsu, Pin-Chia; Samsudin, Firdaus; Shearer, Jonathan
- The Journal of Physical Chemistry Letters, Vol. 8, Issue 22
HIV-1 Assembly Differentially Alters Dynamics and Partitioning of Tetraspanins and Raft Components
journal, September 2010
- Krementsov, Dimitry N.; Rassam, Patrice; Margeat, Emmanuel
- Traffic, Vol. 11, Issue 11
Dynamic multiple-target tracing to probe spatiotemporal cartography of cell membranes
journal, July 2008
- Sergé, Arnauld; Bertaux, Nicolas; Rigneault, Hervé
- Nature Methods, Vol. 5, Issue 8
Dynamics of Crowded Vesicles: Local and Global Responses to Membrane Composition
journal, June 2016
- Holdbrook, Daniel A.; Huber, Roland G.; Piggot, Thomas J.
- PLOS ONE, Vol. 11, Issue 6
Organization, dynamics, and segregation of Ras nanoclusters in membrane domains
journal, May 2012
- Janosi, L.; Li, Z.; Hancock, J. F.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 21
Computational ‘microscopy’ of cellular membranes
journal, January 2016
- Ingólfsson, Helgi I.; Arnarez, Clément; Periole, Xavier
- Journal of Cell Science, Vol. 129, Issue 2
Membrane stiffness is modified by integral membrane proteins
journal, January 2016
- Fowler, Philip W.; Hélie, Jean; Duncan, Anna
- Soft Matter, Vol. 12, Issue 37
Characterization of the motion of membrane proteins using high-speed atomic force microscopy
journal, July 2012
- Casuso, Ignacio; Khao, Jonathan; Chami, Mohamed
- Nature Nanotechnology, Vol. 7, Issue 8
Improved Parameters for the Martini Coarse-Grained Protein Force Field
journal, November 2012
- de Jong, Djurre H.; Singh, Gurpreet; Bennett, W. F. Drew
- Journal of Chemical Theory and Computation, Vol. 9, Issue 1
Lateral Diffusion of Membrane Proteins
journal, September 2009
- Ramadurai, Sivaramakrishnan; Holt, Andrea; Krasnikov, Victor
- Journal of the American Chemical Society, Vol. 131, Issue 35
LINCS: A linear constraint solver for molecular simulations
journal, September 1997
- Hess, Berk; Bekker, Henk; Berendsen, Herman J. C.
- Journal of Computational Chemistry, Vol. 18, Issue 12
The source of high signal cooperativity in bacterial chemosensory arrays
journal, March 2016
- Piñas, Germán E.; Frank, Vered; Vaknin, Ady
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 12
Direct observation of the nanoscale dynamics of membrane lipids in a living cell
journal, December 2008
- Eggeling, Christian; Ringemann, Christian; Medda, Rebecca
- Nature, Vol. 457, Issue 7233
Reduced Lateral Mobility of Lipids and Proteins in Crowded Membranes
journal, April 2013
- Goose, Joseph E.; Sansom, Mark S. P.
- PLoS Computational Biology, Vol. 9, Issue 4
Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes
journal, November 2017
- Duncan, Anna L.; Reddy, Tyler; Koldsø, Heidi
- Scientific Reports, Vol. 7, Issue 1
The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations
journal, July 2007
- Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge
- The Journal of Physical Chemistry B, Vol. 111, Issue 27
Single-molecule imaging of the functional crosstalk between surface NMDA and dopamine D1 receptors
journal, October 2013
- Ladepeche, L.; Dupuis, J. P.; Bouchet, D.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 44
CHARMM-GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides
journal, August 2017
- Hsu, Pin-Chia; Bruininks, Bart M. H.; Jefferies, Damien
- Journal of Computational Chemistry, Vol. 38, Issue 27
Outer membrane of Salmonella typhimurium: chemical analysis and freeze-fracture studies with lipopolysaccharide mutants.
journal, January 1975
- Smit, J.; Kamio, Y.; Nikaido, H.
- Journal of Bacteriology, Vol. 124, Issue 2
Outer membrane of gram-negative bacteria. XVIII. Electron microscopic studies on porin insertion sites and growth of cell surface of Salmonella typhimurium.
journal, January 1978
- Smit, J.; Nikaido, H.
- Journal of Bacteriology, Vol. 135, Issue 2
CASSPER is a semantic segmentation-based particle picking algorithm for single-particle cryo-electron microscopy
journal, February 2021
- George, Blesson; Assaiya, Anshul; Roy, Robin J.
- Communications Biology, Vol. 4, Issue 1
Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane.
text, January 2016
- Fujiwara, Takahiro K.; Iwasawa, Kokoro; Kalay, Ziya
- Apollo - University of Cambridge Repository
A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli
text, January 2016
- Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio
- American Society for Biochemistry and Molecular Biology
Works referencing / citing this record:
Computational simulations of TNF receptor oligomerization on plasma membrane
journal, May 2020
- Su, Zhaoqian; Wu, Yinghao
- Proteins: Structure, Function, and Bioinformatics, Vol. 88, Issue 5
A Multi-Scale Approach to Membrane Remodeling Processes
journal, July 2019
- Pezeshkian, Weria; König, Melanie; Marrink, Siewert J.
- Frontiers in Molecular Biosciences, Vol. 6
Figures / Tables found in this record: