Doug Weibel (U. Wisconsin) "Regulation of bacterial biochemistry at strained bacterial membranes"

Mon, Feb 11, 2013, 12:00 pm to 1:00 pm
Location: 
Joseph Henry Room
Audience: 
Physics faculty, post docs, grads
We are exploring an evolutionarily conserved mechanism for the localization and regulation of biochemistry at strained membranes in bacteria and mitochondria. In this talk, I highlight this mechanism by discussing the regulation of the universal and widely conserved DNA-repair protein, RecA. An emerging picture of bacterial organization is that membrane curvature causes strain in the bilayer that leads to the accumulation of intrinsically curved, anionic phospholipids at the bacterial poles. We have discovered that a large fraction of RecA in Escherichia coli cells is not associated with DNA during normal growth—it is temporally localized at the cell poles through its interaction with anionic phospholipids. Fascinatingly, this interaction inhibits the ATPase activity of RecA, which turns the DNA repair activity of the protein off. When cells are stressed and DNA repair is required, RecA dissociates from the membrane, rapidly diffuses to the mid-cell where DNA is concentrated, and forms active nucleoprotein filaments. We have traced the regulation of RecA function back to the C-terminal region RecA, which forms a known autoregulatory domain. Early studies in this field demonstrated that large amounts of RecA associate with membrane fractions during DNA damage (Garvey et al. 1985, J. Biol. Chem. 285, 18984). A fundamental unanswered question is why does RecA bind the membrane. We have pursued this question using an approach that fuses biophysics, biochemistry, and engineering. Our data supports a model in which the cell prevents unproductive RecA-DNA interactions by storing protein at a DNA-free region of the membrane when its enzymatic function is not required. These and other studies in our lab are enabling us to decode spatial and temporal control of biochemistry in bacteria and mitochondria.
Lunch @ 11:45, talk @ 12-1:00