What role does the movement of hydrogen ions (protons) play in the function of proteins?

The SFB 1078 has set itself the goal of introducing a new mechanistic principle into the understanding of the mechanisms of action of proteins: the control and coordination of complex protein function through protonation dynamics.

The proton movements in the functionally important networks of hydrogen bonds occur on different time and length scales. This ranges from femtoseconds to seconds and from less than 0.1 nanometers to more than 10 nanometers. To better understand the processes, experiments were combined with theory and simulations.

Key Model Protein Systems

Different parts of the protonation dynamics were investigated on two proteins that are important for biological energy conversion: Oxygen reduction, which is coupled to proton pumping by cytochrome c oxidase, and water oxidation, which is catalyzed by photosystem II. It has been found that major structural changes can slow down or even prevent electron transfer in proteins. Light-induced conformational changes play a crucial role in the mechanism of phytochromes, channelrhodopsins and pH-controlled proton channels. The functionality of the latter was compared with that of the pH-controlled viroporins. These changes are often associated with or driven by proton movements.

Development of New Methods for Membrane Bound Proteins

A key aspect of research in the SFB 1078 was the development and adaptation of various experimental and theoretical methods to the requirements of the specific protein systems. These included the incorporation of non-canonical amino acids into proteins, time-resolved serial femtosecond X-ray crystallography, nuclear magnetic resonance spectroscopy at high magnetic fields, time-resolved electronic and vibrational spectroscopy over a large dynamic range, and multiscale modeling approaches from quantum mechanics, molecular dynamics simulation and their hybrids. The application of such advanced techniques to the SFB's proteins was challenging as most of them are integral membrane proteins.

The CRC 1078 achieved its original goal of comprehensively understanding protonation dynamics as an important element of the functional mechanisms of five selected protein families and thus to understand this process as a generic principle of protein function.

Spokesperson

Professor Dr. Holger Dau (2013 - 2017) 

Professor Dr. Joachim Heberle (2017 - 2024)

Involved research groups

Alexiev, Clementi, Dau, Heberle, Heyne, Kozuch, Netz, Schlesinger as well as Block, Imhof, Bondar

Key figures

• € 29.9 m of public funding
• more than 430 publications
• 8 professorial appointments
• 72 doctorates completed

Participating institutions

• Freie Universität Berlin
• Technical University of Berlin
• Technical University of Dresden
• Humboldt University of Berlin
• Charité – Universitätsmedizin Berlin
• Leibniz Institute for Molecular Pharmacology
• Justus Liebig University Giessen
• Hebrew University of Jerusalem in Israel

CRC / SFB 1078

The collaborative research centre investigated molecular switching processes driven by external excitations in well defined molecular systems at solid surfaces. Scientists focused on reversible conformational changes of individual molecules and ensembles leading to measurable changes of functional (e.g. optical, electronic or magnetic) properties of the system. The focus on elementary processes included investigation of all individual steps, physical parameters and interactions which induce and influence the process of molecular switching.

Research grounded on various complementary methods from synthesis of molecular systems, characterization of structural and electronic properties by quantitative surfaces sciences techniques and theoretical modelling. The long-term goals were to develop novel functionalities, like cooperative switching processes, and criteria for applications in molecular functional devices.

Spokesperson

Professor Dr Martin Weinelt, since 7/2015

Professor Dr. Felix von Oppen, till 7/2015

Involved research groups

Brouwer, Fumagalli, Franke, Kuch, von Oppen, Reich, Weinelt, Groß, Pascual, Tegeder

Achievements

• around 430 publications
• 85 doctorates completed
• 5 strategic appointments
• 7 subproject leaders transfered

Participating institutions

• Freie Universität Berlin
• Humboldt University Berlin
• Technical University Berlin
• University Potsdam
• Fritz Haber Institute FHI)
• Paul-Drude-Institut für Festkörperelektronik (PDI)

SFB 658

Nature utilizes protein-cofactor interactions in order to optimize biological functions. The research center focused on the investigation of the interaction of the protein with organic cofactors and metal ions. These interactions were investigated using an approach combining various techniques from molecular biology, biochemistry, structure analysis, spectroscopy and theory.

The collaborative research centre consisted of seventeen scientific projects grouped according to the research goals focussed on the biological processes of electron and excitation energy transfer, conformational changes and signal transduction, and enzymatic cleavage of molecular hydrogen and water oxidation.

Spokesperson

Prof. Dr. Robert Bittl

Involved groups

Research Group Antontik / Stehlik, Research Group Weber, Research Group Haumann / Dau, Research Group Heyne

Participating institutions

• Freie Universität
• Charité - Universitätsmedizin Berlin
• Humboldt University Berlin
• Technical University Berlin
• Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)

The research goal was to learn to control electron and nuclear constellation in different material systems using ultrashort laser pulses. The motion sequences triggered in this way were to be characterized in time and, if possible, guided by appropriate design of the irradiated light fields in such a way that a stable, detectable final state was achieved.

In the first funding period, the focus was on the analysis of such photo-induced dynamic processes, both experimentally and theoretically. The optical excitation of the system was mostly performed with a pump pulse as short as possible, while the resulting change of the nuclear coordinates of the system was interrogated with a sample pulse that was also as short as possible and delayed in time.

In the second funding period, the goal of control was also increasingly realized by using more complex excitation fields. In the experiment, the researchers used suitable modulators for this purpose; complementary to this, the theory of optimal control was expanded. And so, in the area of small, still manageable systems with few active degrees of freedom, there was a very gratifying convergence of theory and experiment, paving an essential part of the way toward more complex systems. Even in the more complex systems, the experimental results, in close cooperation with theory, offered very detailed insights into the dynamics of ultrafast photoinduced reactions.

Spokesperson

Prof. Dr. Ludger Wöste

Participating institutions

• Freie Universität Berlin
• Helmholtz Zentrum Berlin
• The Hebrew University of Jerusalem
• Fritz Haber Institut der Max-Planck-Gesellschaft (FHI)
• Max Born Institute for Nonlinear Optics and Short Pulse Spectroscopy
• Humboldt University  Berlin
• Tel-Aviv University
• University Potsdam

SFB 450

Spokesperson

Prof. Dr Karl-Heinz Rieder

Paricipating institutions

• Freie Universität Berlin
• Humboldt University Berlin
• Technical University Berlin

CRC 290

Spokesperson

Prof Dr Dietmar Stehlik

Funding

DM 37.9 m

Participating institutions

• Freie Universität Berlin: Department of Physics, Department of Chemistry
• Fritz Haber Institute of the Max Planck Society
• Technical University Berlin
• Hahn Meitner Institute

The researchers investigated the electronic structure of interfaces and solid/electrolyte interfaces as well as heterogeneous reactions at interfaces.

Spokesperson

Prof. Bennemann

Funding

DM 25.5m

Participating institutions

• Freie Universität: Department of Physics, Department of Chemistry
• Fritz Haber Institute
• Technical University Berlin

CRC 161 was one of the first collaborative research centers at Freie Universität. The field of work was the investigation of hyperfine interactions in excited nuclear states, molecules, and free atoms, as well as the electronic structure of condensed matter.

Spokespersons

Wilking (1972–73), Hüfner (1973–74), Matthias (1974–75) und Gabriel (1975–86)