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.

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Papers

Elucidation of lipid binding sites on lung surfactant protein A using X-ray crystallography, mutagenesis and molecular dynamics simulations. Boon Chong Goh, Huixing Wu, Michael J. Rynkiewicz, Klaus Schulten, Barbara A. Seaton, and Francis X. McCormack. Biochemistry, 55:3692-3701, 2016.

The water permeability and pore entrance structure of aquaporin-4 channels depend on lipid bilayer thickness. Jihong Tong, Zhe Wu, Margaret M. Briggs, Klaus Schulten, and Thomas J. Mclntosh. Biophysical Journal, 111:90-99, 2016.

Structural refinement of proteins by restrained molecular dynamics simulations with non-interacting molecular fragments. Rong Shen, Wei Han, Giacomo Fiorin, Shahidul M. Islam, Klaus Schulten, and Benoit Roux. PLoS Computational Biology, 11:e1004368, 2015. (19 pages).

Enhanced sampling techniques in molecular dynamics simulations of biological systems. Rafael C. Bernardi, Marcelo C. R. Melo, and Klaus Schulten. Biochimica et Biophysica Acta, 1850:872-877, 2015.

A highly tilted membrane configuration for the pre-fusion state of synaptobrevin. Andrew E. Blanchard, Mark J. Arcario, Klaus Schulten, and Emad Tajkhorshid. Biophysical Journal, 107:2112-2121, 2014.

Synaptotagmin's role in neurotransmitter release likely involves Ca2+-induced conformational transition. Zhe Wu and Klaus Schulten. Biophysical Journal, 107:1156-1166, 2014.

A structural model of the active ribosome-bound membrane protein insertase YidC. Stephan Wickles, Abhishek Singharoy, Jessica Andreani, Stefan Seemayer, Lukas Bischoff, Otto Berninghausen, Johannes Soeding, Klaus Schulten, Eli van der Sluis, and Roland Beckmann. eLife, 3:e03035, 2014. (17 pages).

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, 1837:1769-1780, 2014.

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.