Research Topics - Membrane Biology
Spotlight - The p7 Viroporin
p7 viroporin

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All living systems contain proteins whose job is to move ions across a lipid membrane. Even viruses encode ion transport proteins, which they need to complete their lifecycle and release themselves from infected cells. Such proteins, called viroporins, usually consist of small subunits of one or two helices that can self-assemble in a lipid bilayer into a pore-like structure. Although in some cases, the resulting structures resemble the well-ordered, selective ion channels in higher organisms, often they take on a more disordered character, forming pores with variable numbers of subunits, which adapt their structure and behavior to the environment in which they find themselves. This inherent flexibility and disorder makes it very difficult to produce high-resolution crystal structures of viroporins, which is unfortunate, since they could offer attractive drug targets for new antiviral therapies. Computational modelling and molecular dynamics simulations can help fill in the gaps in our structural knowledge of viroporins, and provide plausible 3-D models for visualization and drug design. In a recent publication, scientists published models of the p7 viroporin found in Hepatitis C virus. MD simulations of these models revealed that p7 can form stable pores with 4 to 7 subunits, with a bias towards 6 or 7 subunits, and that the p7 oligomers are highly flexible in adapting to different membrane thicknesses. These simulations also suggested that specific amino acids in certain places in the structure could play a role in controlling the ion permeability of p7. More details can be found on our p7 website.

All Spotlights


Integration of energy and electron transfer processes in the photosynthetic membrane of Rhodobacter sphaeroides. Michaël L. Cartron, John D. Olsen, Melih Sener, Philip J. Jackson, Amanda A. Brindley, Pu Qian, Mark J. Dickman, Graham J. Leggett, Klaus Schulten, and C. Neil Hunter. Biochimica et Biophysica Acta - Bioenergetics, 2014. In press.

Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Qufei Li, Sherry Wanderling, Marcin Paduch, David Medovoy, Abhishek Singharoy, Ryan McGreevy, Carlos Villalba-Galea, Raymond E. Hulse, Benoit Roux, Klaus Schulten, Anthony Kossiakoff, and Eduardo Perozo. Nature Structural & Molecular Biology, 21:244-252, 2014.

The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex. Antony R. Crofts, Sangjin Hong, Charles Wilson, Rodney Burton, Doreen Victoria, Chris Harrison, and Klaus Schulten. Biochimica et Biophysica Acta, 1827:1362-1377, 2013.

Reconciling the roles of kinetic and thermodynamic factors in membrane-protein insertion. James C. Gumbart, Ivan Teo, Benoit Roux, and Klaus Schulten. Journal of the American Chemical Society, 135:2291-2297, 2013.

The p7 protein of hepatitis C virus forms structurally plastic, minimalist ion channels. Danielle E. Chandler, Francois Penin, Klaus Schulten, and Christophe Chipot. PLoS Computational Biology, 8:e1002702, 2012.

Molecular dynamics investigation of the w current in the Kv1.2 voltage sensor domains. Fatemeh Khalili-Araghi, Emad Tajkhorshid, Benoit Roux, and Klaus Schulten. Biophysical Journal, 102:258-267, 2012.

Viewpoint: An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. Ernesto Vargas, Vladimir Yarov-Yarovoy, Fatemeh Khalili-Araghi, William A. Catterall, Michael L. Klein, Mounir Tarek, Erik Lindahl, Klaus Schulten, Eduardo Perozo, Francisco Bezanilla, and Benoît Roux. Journal of General Physiology, 140:587-594, 2012.

Cytoplasmic domain filter function in the mechanosensitive channel of small conductance. Ramya Gamini, Marcos Sotomayor, Christophe Chipot, and Klaus Schulten. Biophysical Journal, 101:80-89, 2011.

Free energy of nascent-chain folding in the translocon. James Gumbart, Christophe Chipot, and Klaus Schulten. Journal of the American Chemical Society, 133:7602-7607, 2011.

Cryo-EM structure of the ribosome-SecYE complex in the membrane environment. Jens Frauenfeld, James Gumbart, Eli O. van der Sluis, Soledad Funes, Marco Gartmann, Birgitta Beatrix, Thorsten Mielke, Otto Berninghausen, Thomas Becker, Klaus Schulten, and Roland Beckmann. Nature Structural & Molecular Biology, 18:614-621, 2011.