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Investigation of the voltage-dependent anion channel 2 (VDAC2) by solid-state NMR and molecular dynamic simulations

Objective

Voltage-dependent anion channels (VDACs) are pore-forming proteins expressed in the outer membrane of eukaryotic mitochondria. The three isoforms of VDAC, i.e. VDAC1, VDAC2 and VDAC3, are known to be expressed ubiquitously in mammalian mitochondria. The individual VDAC isoforms (VDAC1 and VDAC2) are considered to play different roles in the induction of apoptosis through Bcl-2 family proteins and may also play a role in switching apoptotic signaling, whereas the function of VDAC3 is till date not fully known. In particular VDAC2 has been suggested to play a specific role in regulating apoptosis by interacting with, and thereby preventing activation of, the proapoptotic protein BAK. Solid-state NMR (ssNMR) methods will be used to study the structural aspects of VDAC2 and its interactions with apoptotic proteins. These experiments will be performed on isotope-labeled [13C, 15N] protein variants, from which resonance assignments and structural restraints of VDAC2 in lipid bilayers will be obtained. As a complementary method, the molecular simulations (MD) will be performed to study first the homology model on VDAC2 based on the VDAC1 structure, and finally used as the comparison to the ssNMR data. In the MD part the function and interaction mode of the N-terminal helix is of the main interest. In general, the goal of this project is to characterize the structure and dynamics of VDAC2 and to understand its role as an anion channel in the outer mitochondrial membrane in apoptosis and possibly neurodegeneration.

Call for proposal

FP7-PEOPLE-2009-IEF
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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Address
Hofgartenstrasse 8
80539 Munchen
Germany

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Activity type
Research Organisations
Administrative Contact
Manfred Messerschmidt (Mr.)
EU contribution
€ 161 661