A Talk on ‘Protein Dynamics and Kinetics studied by NMR Spectroscopy’ by Professor Christian Griesinger

ABOUT THE TALK
NMR spectroscopy is a powerful tool to study the dynamics and kinetics of conformational
ensembles. While pico-second to single digit nano-seconds timescales are well covered by relaxation measurements, and several (> 10) micro-seconds to milliseconds by relaxation dispersion, relying on the variation of isotropic chemical shifts, the region between one-digit nano-seconds and several 10 micro-seconds is difficult to access. High power relaxation dispersion can assess the amount and kinetics of motion in this region. This will be discussed in the context of protein motion and protein/protein recognition with approaches to get information about the region between nanosecond and microsecond. The importance of optimal control pulses for high-field NMR of proteins will be emphasized. The second topic will be on the signal transduction of two-component systems. They are the GPCRs of bacteria. The sensory part is a dimer that receives the signal on the periplasmic side, and transmits it through the membrane to the cytosolic side. This induces cross phosphorylation of histidine kinases which form one subunit of the sensory protein. The cross-phosphorylation happens only in the activated state. In the case of the citrate sensor, two conformational states can be identified, with and without citrate. Transmembrane signaling due to citrate binding will be discussed.

In the third project, we studied the process of aggregation of α-synuclein on membranes in vitro. We identified key time points in the aggregation process that enable targeted isolation of a so-called intermediate 1 and the fibrillar endpoint. Intermediate 1 has the functional characteristics of a toxic oligomer, and the structure will be presented. In addition, we determined the structure of anle138b, a clinical drug candidate, bound to
lipidic fibrils that are doped with anle138b as compared to a PET candidate.
A comparison of the binding of this molecule to lipidic Ab fibrils will be discussed

ABOUT THE SPEAKER
Christian Griesinger, Dr. phil., is author of more than 310 publications. He studied chemistry and physics and received a PhD in chemistry in 1986. After a postdoctoral fellowship at the physical chemistry laboratory of ETH Zürich with later nobel laureate Richard Ernst, he was appointed (1990) as full professor of organic chemistry at University of Frankfurt and as director at the Max Planck Institute for Biophysical Chemistry (1999). He develops methods in nuclear magnetic resonance and applies them to structure investigations of small molecules and proteins, specifically intrinsically disordered proteins such as alpha-synuclein, a key player in Parkinson’s disease. Modifying alpha-synuclein’s structures by small molecules lead to the joint research program with Dr. Armin Giese and the discovery and patenting of anle138b and the co-founding MODAG GmbH in 2013. He was awarded the Sommerfeld (1997), Leibniz (1998), Bayer (2003), Elhuyar-Goldschmidt (2011), Bücher (2012) and Ampere (2014) prizes and an ERC advanced grant (2008).

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