Dynamics and Assembly of membrane proteins

A larger system we are studying is the bacterial photosynthetic system. This simple system forms specialized membranes composed essentially of 3 to 4 intergal membrane complexes. The different proteins are able to assemble spontaneously into specialise membranes within the bacteria, the morphology and composition of these domains are important for function, and we try to understand why certain proteins assemble into these domains and how their internal structure is determined.

Currently we are using multiple methods to modify the organization of membrane components, using molecular biology tools to modulate expression of the different components in living bacteria and constructing artificial photosynthetic systems bottom up. In both cases we study the organization and function of the system in order to elucidate the links between structure and function and the robustness of this simple integrated biological system.

The Voltage-Dependent Anion Channel (VDAC) is the most abundant protein in the OMM. Its three isoforms form β-barrel porins governing the flux of ions and metabolites between the organelle and the cytosol. Although VDAC’s transport function has been thoroughly studied, its role in mitochondrial regulation, as well as the function of eachisoform, remains elusive.

Numerous recent studies showed that interactions between pro-apoptotic Bax and Bak and VDAC are necessary to trigger cyt c release and the apoptosis cascade. Very limited data is available on the molecular mechanism of cyt c permeation. The characterization of the interaction between VDAC and Bax/Bak, and the complex(es) composition, formation or regulation are critical pieces missing to understand the molecular mechanism of this key event of apoptosis.

Our research focuses on identifying the exact composition, structure and regulation of VDAC and Bax/Bak pro-apoptotic complex(es). We use a combination of biochemical, biophysical (DEER, nMS, EM) and computational methods to investigate VDAC’s role in mitochondria-mediated apoptosis. This will expand our collective understanding of how these complexes assemble and trigger apoptosis, and establish hypothesis on the molecular mechanism behind cyt c release.