New publication in J. Phys. Chem. B

Together with our colleagues at the Institute for Biophysical Dynamics at the University of Chicago, we have developed a method using infrared spectroscopy and atomistic modeling that would allow to better understand the mechanism behind the extreme ion selectivity and transport properties in ion channels. Our findings have recently been published in The Journal of Physical Chemistry B.

Location of the potassium channel KcsA in the cell membrane of bacteria. The schematic illustration on the right shows the changes in strength and direction of vibrational coupling inside the filter depending on the ion species, as found by the study. @David S. Goodsell & RCSB Protein Data Bank

Location of the potassium channel KcsA in the cell membrane of bacteria. The schematic illustration on the right shows the changes in strength and direction of vibrational coupling inside the filter depending on the ion species, as found by the study. @David S. Goodsell & RCSB Protein Data Bank

Ion channels are essential structures of life.

Ion channels are specialized pores in the cell membrane and move charged atoms known as ions in and out of cells, thereby controlling a wide variety of biological processes including brain function and heartbeat. Ion channels are generally selective for certain ions, allowing specific types of ions to flow through at very high rates, while hindering the flow of others. On the basis of this selective permeability, ion channels are classified as potassium channels, sodium channels, etc.

The cell’s most ubiquitous gateways are potassium ion channels – the importance of this type of ion channels was underpinned in 2003 when Roderick MacKinnon received the Nobel Prize in Chemistry for resolving the first atomic structure of the bacterial KcsA potassium channel.

Despite a large body of work, the exact molecular details underlying ion selectivity and transport of the potassium channel remain unclear. Since conventional methods, such as X-ray crystallography, capture only averaged frozen structures, it is not possible to investigate how the dynamic of the protein could be involved in key aspects of their function.

New method to unravel the secret of ion channel selectivity

Our team, together with researchers at the Institute for Biophysical Dynamics (University of Chicago), have now used infrared (IR) spectroscopy coupled with molecular dynamic-based simulations of the obtained spectra to investigate the subtlest changes in the shape of the KcsA potassium channel that are induced by binding either potassium or the only 0.04 nanometers smaller sodium ion. This combination proved to be a powerful tool to disentangle convoluted IR spectra – which contain contributions from the whole protein – by assigning each part of the spectrum to the amino acids that contribute to it.

This new approach allows us to probe these mechanisms in a non-perturbative way, meaning without tedious and expensive isotope labeling strategies. Moreover, it opens the way to study the structure and dynamics of ion channels on their biologically relevant timescales by extending it to two-dimensional infrared spectroscopy.

The study shows for the first time that the combination of the two methods can be used to detect subtle conformational changes in large membrane proteins, such as the KcsA potassium channel. Furthermore, it opens the way to capture the dynamics of proteins in real time at atomic resolution, which has been impossible with standard techniques until now.

Read the publication or browse through our other publications.

Press releases about the topic by the MFPL and IMP.

Paul Stevenson, Christoph Götz, Carlos R. Baiz, Jasper Akerboom, Andrei Tokmakoff, and Alipasha Vaziri
Visualizing KcsA Conformational Changes upon Ion Binding by Infrared Spectroscopy and Atomistic Modeling
J. Phys. Chem. B 2015, 119 (18), pp 5824–5831 (Download)

New Publication in Analytical Chemistry

Together with our collaborator Markus Arndt we published in Analytical Chemistry on how to improve Laser-induced acoustic desorption (LIAD) for natural biochromophores. This methodology might enable us to use fragile biomolecules in Quantum-enhanced metrology experiments.

Link to Paper or look up other publications of our group.

Ugur Sezer, Lisa Wörner, Johannes Horak, Lukas Felix, Jens Tüxen, Christoph Götz, Alipasha Vaziri, Marcel Mayor, and Markus Arndt
Laser-induced acoustic desorption of natural and functionalized biochromophores
Anal. Chem., 2015, 87 (11), pp 5614–5619 (Download)

New Paper in eLife on a Non-Conventional Translocation Mechanism for Motor Proteins

Motors proteins of the conserved kinesin-14 family have important roles in mitotic spindle organization and chromosome segregation. Previous studies have indicated that kinesin-14 motors are non-processive enzymes, working in the context of multi-motor ensembles that collectively organize microtubule networks. Here we show that the yeast kinesin-14 Kar3 generates processive movement as a heterodimer with the non-motor proteins Cik1 or Vik1. By analyzing the single-molecule properties of engineered motors we demonstrate that the non-catalytic domain has a key role in the motility mechanism by acting as a ‘foothold’ that allows Kar3 to bias translocation towards the minus end. This mechanism rivals the speed and run length of conventional motors, can support transport of the Ndc80 complex in vitro and is critical for Kar3 function in vivo. Our findings provide an example for a non-conventional translocation mechanism and can explain how Kar3 substitutes for key functions of Dynein in the yeast nucleus.

See more on the eLife Homepage or on our Website.

New publication in Nature Methods

Our recent paper on “Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy” was published today in Nature Methods. Using light-field deconvolution microscopy for functional biological imaging, we were able to simultaneous  record the activity of the entire nervous system of C. elegans and showed whole brain imaging in zebrafish larvae at 20Hz volume rate.  Click here for further information.

New Publication in Nature Methods

Our recent paper on “Brain-wide 3D imaging of neuronal activity Caenorhabditis elegans with sculpted light” was published today in Nature Methods.

Here, we introduce wide-field temporal focusing (WF-TEFO), a two-photon technique, which is based on light-sculpting and enables recording the activity of the majority of neurons in the head ganglia of C. elegans with high temporal and spatial resolution.

Click here to read the abstract or browse the research section on our homepage, to read more about the new technique which enables neurobiologists to acquire realtime 3D-videos of active neurons (see video below).

New Nature Publication online

We are happy to announce, that David Cisneros – a shared Postdoc of our group and the lab of Jan-Michael Peters at the IMP Vienna – has contributed to a recent Nature publication which sheds light on the organization of chromosome structure and segregation:

Wapl is an essential regulator of chromatin structure and chromosome segregation

These findings reveal that the stability of cohesin–DNA interactions is an important determinant of chromatin structure, and indicate that cohesin has an architectural role in interphase chromosome territories.

New review paper published

Recently, a review paper entitled “Reshaping the optical dimension in optogenetics” by Alipasha and his collaborator, Valentina Emiliani from the CNRS in Paris, got published in Current Opinion in Neurobiology. In the paper, they discuss and compare the main new optical techniques that have become available in recent years in the field of optogenetics. The paper can be accessed by clicking here.