Function of a novel SPFH domain protein in bacteria

• Applicant: Professor Dr. Marc Bramkamp
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Cell Biology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 414320409

Bacterial cells are surprisingly compartmentalized into functional areas and domains. This compartmentalization includes the plasma membrane. Research from several laboratories, including mine, has shown that scaffold proteins such as flotillins help to organize the membrane into functional domains. Also several cellular processes are thought to rely on this membrane compartmentalization the precise molecular mechanisms are still rather elusive. Flotillins share a signature sequence that has been termed SPFH domain. This protein domain is found in stomatins, prohibitions, flotillins and the bacterial HflK/C proteins. In all cases the SPFH domain has been shown to contribute to protein oligomerization, likely a necessity to function as molecular scaffold. Research on bacterial flotillins has gained a tremendous interest in recent years because null mutations or chemical inactivation of flotillin assembly has pleiotropic effects on cells and leads to impaired functions in biofilm formation and cellular growth and differentiation. Flotillins exclusively associate with highly ordered membranes and hence it was proposed that these SPFH proteins are marker proteins for so-called lipid rafts. We have recently discovered a new member of the SPFH domain family of proteins in Bacillus subtilis. Our preliminary work revealed that this protein localizes to liquid disordered membrane regions and that it is involved in cellular stress response. Genetic and proteomic analyses revealed a tight link of this novel SPFH protein to the general stress response pathway and to cell envelope stress. Unlike flotillins, this SPFH domain protein does not bind to the plasma membrane itself, but requires tow membrane integral proteins that are encoded in the same operon. The membrane complex only assembles under stress conditions and we hypothesize that this complex plays a central role in the perception and response to external cell envelope stress in bacteria.

• DFG Programme: Research Grants