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Content archived on 2022-12-23

Structure and function of proton-pumping membrane proteins, especially nicotinamide nucleotide transhydrogenase

Objective



Membrane proteins often catalyze transport processes in which the driving force is derived from reduction-oxidation processes. These redox-reactions are linked to conformational changes which, in turn, drive membrane transport. One of the very best examples of such proteins is the transhydrogenase, a widely distributed and essential enzyme, which mechanistically may serve as a model system for similar but more complex systems.
The groups of Rydstrom and Jackson have recently contributed considerably to the progress of this important area of research. Based on the cloning of several transhydrogenase genes, over-expression of these genes, characterization and reconstitution of purified transhydrogenases and structural predictions based on similarities between (di)nucleotide- dependent soluble and membrane proteins, the amount of information about the transhydrogenase system has now reached a level where relevant structure-function questions may be asked.
The objective of the present proposal is to provide a further understanding of the detailed structure of primarily the membrane sector containing the proton-conducting structure of transhydrogenase, but also other domains such as the domains binding NAD(H) and NADP(H). These aspects are of paramount importance for the understanding of the structure-function relationships of these domains and eventually for the understanding of the mechanism of proton pumping by transhydrogenases and related enzymes.
In this context, experience and modern methods in mollar biology, immunology and biochemistry related to membrane proteins are essential for the progress of the project. This expertise is represented by the groups of Shakhparonov and Grinkevich, and the traditionally strong and competent environment at the Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry and Moscow State University, respectively.
Results produced within the framework of the program will be published as original scientific articles and presented/discussed at special meetings planned for the member groups of the proposal.
The collaboration will provide the basis for a more long lasting exchange of information, further collaborations and exchange of students between western and Russian research groups.

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Coordinator

Goteborg University
EU contribution
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Address
Medicinaregatan 9C
413 90 Göteborg
Sweden

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Total cost

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Participants (3)

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