Technical University of Munich, Institute of Structural Biology, Germany
Bcl2 proteins govern the intrinsic pathway of apoptosis at the outer mitochondrial membrane (OMM). The concentration ratio of the individual Bcl2 family members determines whether large pores are formed to release pro-apoptotic inducers, such as cytochrome C. To enable or inhibit pore formation, Bcl2 proteins must be located at the OMM surface, which induces large conformational changes in pore-forming Bcl2 proteins upon activation. We have developed biochemical tools for studying membrane proteins in a native lipid environment by structural methods and in particular NMR, which is a crucial factor for this conformationally labile protein class. This talk will cover recent developments in my lab on membrane protein structural biology using so-called lipid nanodiscs – a self-assembling native lipid membrane mimetic – as well as protein ligation tools that can be used for segmental isotope labeling for NMR. Furthermore, I will share (un)-published structural insights on Bcl2 protein structure determination, activation, and complex formation at the membrane surface. In addition, I will discuss unpublished work on mechanistic details of apoptosis induction by the voltage-dependent anion channel subtype 1 (VDAC-1).
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