Alessandro Senes, Professor, Biochemistry, University of Wisconsin-Madison, will give a talk on "Understanding membrane protein complexes with a computational and experimental strategy."

ABSTRACT

The general focus of our laboratory is understanding the folding, structure, and function of membrane protein complexes using a combination of biophysical methods and computational modeling. A major system of interest are membrane proteins of the divisome, the complex that governs cell division in bacteria. In particular, we are interested in a key regulatory complex. FtsLB interacts with the peptidoglycan synthase machinery, triggering the reconstruction of the cell wall necessary for cell separation.  The structure and mechanism of action of FtsLB are not known but using computational modeling in integration combination with biophysical, biological, and bioinformatics methods, we have developed a structural model of the complex. Our data indicate that FtsLB is a tetrameric helical bundle in the membrane region and it splits into a pair of coiled coil domains as it extends into the periplasm. The model reveals a number of unusual structural features that may be important for its function. In particular, the coiled coil is unusually rich of polar residues in its core, a characteristic that makes this domain marginally stable and likely dynamic. This conserved feature is important for fine-tuning the structural balance between the off and on states of FtsLB. The research exemplifies how computational structural methods can guide the experimental study of difficult-to-solve membrane protein complexes.