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A01: The hemolysin secretion machinery of E. coli

Protein translocation by type 1 secretion systems (T1SS) of Gram-negative bacteria is achieved in a single step directly from the cytosol into the extracellular space. The translocation machinery is composed of three core proteins, two of which reside in the inner membrane and belong to the ABC transporter and membrane fusion protein families. The third component, a porin-like protein, is located in the outer membrane. All T1SS contain the information necessary and sufficient for secretion at their extreme C-terminus. The best-characterized example is the hemolysin A (HlyA) machinery present in uropathogenic E. coli strains. A dynamic assembly of the three transport proteins is induced upon interaction with the substrate, which results in the formation of a continuous channel ranging from the inner membrane to the exterior. Despite the knowledge of the components and the overall architecture of this nanomachinery, we know little about the underlying coordination in space and time. Thus, the molecular details, which trigger a switch in the molecular identity (receptor-like, transporter and channel) of the components into a secretion-competent state, are largely unknown. Additionally , the molecular dynamics and switches, which result in channel formation, remain enigmatic. Within the framework of the CRC we aim to relate the dynamic assembly of the translocation complex with the molecular identity of the transport-competent components of this machinery.  This requires a combination of structural and functional approaches with cellular studies and will not only provide new molecular insights in the underlying temporal and spatial organization of a T1SS, but also determine general principles of protein transport and molecular cross-talk within multi-membrane protein systems.

Project leader: Prof. Dr. Lutz Schmitt

Associated leader: Prof. Dr. Sander Smits

Researchers: Manuel Anlauf, Florestan Bilsing, Eymen Hachani, Cigdem Günes