Protein dynamics: Molecular machines at work | 10/8/2018 | Staff
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Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich have used a special fluorescence-based imaging technique to track the shape changes that occur when pore proteins in the cell membrane export molecules into the extracellular medium.

A biological cell can be thought of as a hive, in which proteins are the worker bees. However, proteins are far more versatile and can interact with each other to form molecular machines. In order to understand the mechanisms that underlie their functional versatility, structural biologists have relied primarily on the analysis of their three-dimensional structures following crystallization.

Crystals - Picture - Approach - Thorben - Cordes

However, protein crystals provide an essentially static picture. "So this approach on its own is insufficient," says Thorben Cordes, professor of Physical and Synthetic Biology at LMU. "We need to understand the molecular motions and the structural alterations that take place in proteins in the course of their operation." Cordes and his research group have concentrated on finding ways to visualize protein dynamics. In cooperation with teams at Imperial College London and the University of Groningen, they have characterized the conformational changes that occur in a class of membrane-integrated transport proteins. The new findings appear in the EMBO Journal.

The researchers focused on what are called ABC transporters, essential membrane proteins that are involved in many cellular processes, including nutrient uptake, detoxification and immune reactions. All ABC transporters are made up of two modules. A transmembrane domain, which is embedded in the membrane, forms the pore through which the substrate is exported from the cell. The intracellular nucleotide-binding domain is responsible for supplying the required energy—which it does by binding and breaking down ATP, the cell's major carrier of chemical energy.

Order - ABC - Substrates

In order to determine how ABC transporters actually dispatch their substrates across...
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