Metabolic Coordination Through Metabolite-Protein Interactions

Dr. Uwe Sauer

Institute of Molecular Systems Biology, ETH Zurich, Switzerland


How do bacteria know what goes on in their environment and how do they make appropriate decisions? While some bona fide extracellular sensors are known, there are far more environmental conditions and cellular responses than could possibly be dealt with through dedicated sensors. Instead, most microbial responses are based on direct intracellular consequences of environmental changes. One of the first affected networks to just about any extracellular change is metabolism that passively responds to nutritional or chemical/physical challenges. Since fluxes and intracellular metabolite levels respond within seconds, allosteric binding of metabolites to regulatory proteins and enzymes is a highly effective and rapid sensing mechanism. Different from well-establish methods to assess physical interaction between proteins and between proteins and nucleic acids, however, methods to assess metabolite-protein interactions are still in their infancy. At present we know on the order of 1500 unique regulatory metabolite-protein interactions (1). I will present results on experimentally mapping this network out further in E. coli. The current results indicate that the known interactions are only the tip of the iceberg (2). Beyond mapping the regulation network, I will focus on the even more challenging and conceptual problem: understanding which of the many regulation mechanisms actually matter for a given adaptation to elicit an appropriate physiological response. The surprising result is that only very few regulation events appear to be required for a given transition, typically involving less than a handful of active regulators (3).

  1. Reznik, Christodoulou, Goldford, Briars, Sauer, Segre & Noor. Cell Reports 20: 2666-2677 (2017).
  2. Piazza, Kochanowski, Cappelletti, Fuhrer, Noor, Sauer & Picotti. Cell 72:358-372 (2018).
  3. Kochanowski, Gerosa, Brunner, Christodoulou & Sauer. Molecular Systems Biology 13: 903 (2017).

Date: Oct 18, 2019 (Fri) 17:00—18:30
Place: Faculty of Science Bldg.3, 4F, room 412
Host: Shinya Kuroda (skuroda AT bs.s.u-tokyo.ac.jp)