Research Topics - Membrane Biology
Spotlight - Lactose permease
Opening of Lacy'S cytoplasmic cavity

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Escherichia coli are bacteria living in the intestines of mammals as part of their healthy gut flora, but also causing disease outside of the gut. The bacteria import from their environment nutriments, for example molecules of lactose, a sugar. For this purpose Escherichia coli employs in its cell membrane a protein channel, lactose permease, that translocates the sugar outside-in. This is the bacterium's "sweet tooth". To establish the unidirectional sugar transport, the bacterium utilizes an electrical potential maintained in the form of a trans-membrane proton gradient (more protons on the outer cellular than on the inner cellular side of the membrane). Protons, very small ions, that enter the channel from the outside one at a time, open the outer channel entrance. This permits access of lactose that gets bound inside the channel. Release of the proton to the cell interior closes the outer channel entrance and opens the inner channel entrance, such that the bound lactose can enter the cell. Despite extensive and elegant biochemical studies, the physical mechanism that couples unidirectional proton and sugar translocation is not yet known in detail. A crystallographic structure of lactose permease permitted now investigations into this mechanism by means of molecular dynamics simulations using NAMD. The simulations, reported in a recent publication, showed one step of the proton - sugar translocation, namely how binding and unbinding of the proton activates a spring-like bond, a so-called salt bridge, that closes and opens the inner channel exit. More information on the lactose permease project can be found here.

All Spotlights

Papers

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.

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.