Highlights In The November Issues Of Biophysical Journal

Main Category: Medical Devices / Diagnostics
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Article Date: 01 Nov 2007 - 5:00 PDT

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The November 1st and November 15th issues of Biophysical Journal, published by the Biophysical Society, are now available online. Topics of interest include voltage-gated potassium channels that could payoff in synthetic drug design, the absence of large lipid rafts in cells, and the structure of a Na+/H+ antiporter dimmer.

Volume 93, Issue 9, November 1, 2007

Dynamics of the Kv1.2 voltage-gated K+ channel in a Membrane Environment

Vishwanath Jogini, University of Chicago and Benoit Roux, University of Chicago

Using powerful computers at Argonne National Laboratory, scientists have taken a step closer to understanding how voltage-gated potassium channels work. Vishwanath Jogini and Benoît Roux, researchers in the University of Chicago's Institute of Molecular Pediatric Science, used the large-scale computers in Argonne's Laboratory Computing Resource Center to conduct simulations of the channels in mammalian cells.

The features revealed by these computer simulations could lead to medical breakthroughs in synthetic drug design.

Specifically, Jogini and Roux produced molecular dynamic simulations of a detailed atomic model of the Kv1.2 voltage-gated potassium channel in an explicit membrane using the crystallographic x-ray structure determined by Rod MacKinnon (Rockefeller University) and his collaborators in 2005.

A long-term endeavor of biophysical research is to advance our understanding of these proteins and predict their function. The voltage-gated channels regulate the generation and spread of electrical signals in neurons, muscles, and other excitable cells. These minuscule electrical signals carry nerve impulses and control muscle contractions.

In humans, malfunction of these channels can result in neurological or cardiovascular diseases, such as cardiac arrhythmia.

Why are lipid rafts not observed in vivo?

Arun Yethiraj, University of Wisconsin and James C. Weisshaar, University of Wisconsin

The cell membrane consists of many types of lipid and protein molecules. Some years ago the existence of "lipid rafts," domains enriched in particular lipid molecules, was postulated. Many functions of the cell, including transport of matter from the outside (endocytosis) and signaling, during which specific proteins are gathered in a small area, have been attributed to rafts. The very existence of rafts in live cells, however, is hotly debated and direct evidence of rafts in vivo is sparse. While large rafts are readily observed in artificial membranes, attempts to observe analogous domains in live cells place an upper limit of 5 nanometers on their size.

In this paper Yethiraj and Weisshaar propose a new idea for why large rafts might not be present in cells. They suggest that proteins that span the membrane act as immobile obstacles, and show that the presence of these obstacles limits the size of lipid domains that can be formed. The presence of obstacles at only 5-10% by area suppresses the formation of large domains seen in artificial membranes. The structural and spatial heterogeneity of the membrane thus plays a crucial role in its biophysical properties.

Volume 93, Issue 10, November 15, 2007

High-resolution structure of a Na+/H+ antiporter dimer obtained by pulsed EPR distance measurements

Daniel Hilger, LMU Munich; Yevhen Polyhach, University of Konstanz; Etana Padan, Hebrew University of Jerusalem' Heinrich Jung, LMU Munich' and Gunnar Jeschke, University of Konstanz

Our current knowledge about the molecular basis of life mainly stems from the determination of structures of the molecules of life, for instance proteins, DNA, and RNA. However, living cells largely function through the formation of short-lived complexes between such molecules, and in many cases such complexes are not accessible to existing approaches for structure determination. We introduce a new, broadly applicable approach that is based on distance measurements in the nanometer range between sites in the component molecules by pulsed electron paramagnetic resonance spectroscopy. This approach can provide highly resolved structures of biomacromolecular complexes if the structures of the components are known beforehand. It is applied to a dimer of the membrane transport protein NhaA, which is responsible for regulation of the intracellular pH in cells of Escherichia coli. Since the function of NhaA critically depends on dimerization, the dimer structure provides new insight into the mechanism of ion transportation through cell membranes by this protein.

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Article adapted by Medical News Today from original press release.
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Abstracts for these articles can be found at http://www.biophysj.org/.

Source: Ellen R. Weiss
Biophysical Society