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Proteins are the molecular machinery of life. As nanomachines of metabolism, they are in every cell of our body tirelessly active, transport, synthesize, divide and transform substances. The ability of specific proteins to do their job is determined by the sequence of amino acids and their three-dimensional arrangement, but also depends on structural rearrangements dependent on the environmental conditions.

Protein dynamics

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To perform their function structural changes are often important. They reach from atomic reorientation to rearrangements of complete domains to enclose substrates, to release products or to reconfigure domains in complexes. Neutron Spin Echo Spectroscopy is a versatile tool to investigate these large scale movements in biomolecules on different length scales with the ability to determine the timescale of the motions. The proteins can be examined in a D2O buffer solution, which is close to the natural conditions. Also neutron scattering does not destroy the proteins. In recent studies we found large scale motions of complete domains in yeast alcohol dehydrogenase and phosphoglycerate kinase.

R. Biehl

Intrinsically unstructured proteins and disordered regions


A large class of proteins has not a defined tertiary structure. These proteins have structured parts (or not) connected by disordered regions with high degree of configurational freedom. This class challenges the traditional structure-function paradigm. The IUP's sometimes fold upon binding to an active configuration e.g. in conjunction with other molecules. The dynamics is important to understand the structuring process prior to function, the dynamics of folding or the function as an unstructured protein itself. Two approaches can be used to elucidate the underlying phenomenons. Structured proteins can be partly unfolded (e.g. temperature) to examine intermediate stable unfolded intermediates or intrinsically unfolded proteins can be examined directly. As an extreme case a complete unstructured protein should behave as an stiff random polymer chain.

R. Biehl

Structure of protein denatured states

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Protein folding intermediates can be trapped chemically (denaturing agent, pH, ionic strength) as well as physically (temperature and pressure). Small Angle Neutron Scattering techniques allow to access protein structural intermediates as a function of temperature up to 120°C and as a function of pressure up to 5000 bar with the new high pressure set-up available at JCNS. The figure presents the Kratky plot of the scattered intensity for a myoglobin protein under chemical denaturing conditions. Besides protein folding intermediates characterization, we are investigating ligand binding effect on protein structure stability upon denaturation.

M.-S. Appavou

Protonation states of proteins

Knowing the three dimensional structure of a protein is a pre-requisite for understanding its function Protein x-ray crystallography is a well established tool to obtain structural information on proteins. However, with x-rays as probes the position of hydrogen atoms can hardly be seen.
Here, neutron scattering on protein crystals opens up the possibility to locate hydrogen atoms even at moderate resolutions of 2 Å. Therefore, in collaboration with the FRM II in Garching the BioDiff, a dedicated instrument for neutron protein crystallography is being built. A first measurement of Bragg-reflections from a sperm whale myoglobin crystal with the CCD-detector of the BioDiff instrument is shown in the first picture on the left. The resulting protein structure is depicted in the picture on the right. The additional information gained with neutron protein crystallography is for example the identification of unusual hydrogen bonds, the protonation state of side chains and the solvent structure around the protein, just to name a few.

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Tobias E. Schrader


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