Welcome to the Henzler-Wildman Lab
Integral membrane proteins control to the movement of molecules and signals across the membrane. To fully understand the function of these dynamic proteins requires knowledge of the timescale, amplitude, and direction of structural changes. We use nuclear magnetic resonance (NMR) as our primary technique to monitor protein structure and dynamics, taking advantage of the extensive resources available through the National Magnetic Resonance Facility at Madison (NMRFAM). By comparing our NMR data with biochemical and functional assays, we gain insight into the mechanisms of secondary active transport, multidrug recognition, ion channel gating and ion selectivity.
EmrE and other small multidrug resistance (SMR) transporters
Our research on EmrE focuses on three distinct themes:
- The multidrug activity of EmrE – How does such a small transporter recognize and transport such a diverse class of substrates?
- The mechanism of secondary active transport – How are proton and substrate transport coupled so that the proton motive force can be harnessed to drive drug efflux? How do some substrates trigger uncoupled transport or leak pathways?
- The native function of EmrE – The small multidrug transporter family includes both apparent multidrug efflux pumps, like EmrE, and more specific transporters of guanidinium or other metabolites. What features define members of each class and how did this family evolve to include such diverse functions?
NaK, a bacterial non-selective cation channel
The NaK project investigates the role of protein dynamics in the molecular mechanism of ion selectivity, gating, and coupling between the inner gate and selectivity filter.
We are collaborating the with the Kirchdoerfer and Rienstra labs to study the structure and dynamics of a subset of proteins from SARS-CoV-2.