Thursday at 12PM during the academic year
Dana Yaffe won many awards this year:
Rahamimoff Travel Grants Program for Young Scientists - BSF
SMART prize for "paper of the month" of the Silberman institute
ASBMB graduate student travel award
Esmeralda Z. Reyes-Fernández, a new postdoc in the lab joined us from Mexico after a Ph.D. at Max Planck Research School for Environmental, Cellular and Molecular Microbiology (IMPRS-Mic), Marburg, Germany
Prof. Shimon Schuldiner
MY LATEST RESEARCH
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Vesicular monoamine transporters (VMATs) are the targets of numerous psychoactive drugs and play a critical role in the overall process of synaptic transmission by replenishing depleted monoamine stores in synaptic vesicles. They transport monoamines in a process that involves exchange of 2H+ per substrate. Here we show that two potent inhibitors of VMAT2, tetrabenazine and reserpine, bind to different conformations of the protein. The transition between these conformations requires the generation of a proton gradient across the membrane. Here we emulate the effect of the proton gradient by tinkering with residues that form the cytoplasmic gate. These findings provide vital information about the conformational dynamics of a mammalian H+-coupled antiporter. Such conformational transitions constitute essential steps in all transport processes.
Antibiotic resistance is a growing global public health concern and was recently defined by the Center for Disease Control as among the most urgent problem facing physicians today. We show here that multidrug transporters are essential for acquisition of high-level, clinically significant antibiotic resistance. To achieve high-level resistance, multiple mutations accumulate sequentially, each providing a small but distinct increase in fitness. Transporters decrease the cytoplasm concentration to values that allow fixation of single mutations. We identified transporters that are essential for the acquisition of resistance to quinolones, we different types of transporters work in a concerted mode and we show that the function of the major transporter AcrAB-TolC can be partially backed up by other TolC-dependent ones.