Function of Membrane Enzymes in their Native Lipid Environment

The coupling between the complex membrane environments and its affiliated membrane enzymes is among the most exciting and challenging puzzles of cellular function. Membrane proteins function in a dynamic material, where the membrane physiochemical conditions (e.g. composition, charge, fluidity, lateral pressure profile, phase separation) govern their reactivity. Reactivity is broadly defined as the ability to form stable associations, maintain and interconvert between active conformations matched to the lipid bilayer properties, and access hydrophobic substrates. It also encompasses the requisite to find protein partners, assemble multi protein machineries, localize into designated lipid domains and generate variable membrane shapes. Therefore, function of membrane proteins spans multiple length scale and organization levels. Our goal is to relate molecular information to the microscopic, heterogeneous environment in which membrane proteins function to ultimately arrive at a comprehensive understanding of membrane proteins function.

My group studies the contribution of the membrane properties to the high specificity and rate enhancement of membrane enzymes. We seek to understand the general principles that drive membrane proteins to form stable membrane associations, maintain and interconvert between active conformations matched to the lipid bilayer properties, and access hydrophobic substrates. To experimentally address these diverse questions my lab employs solid and solution-state nuclear magnetic resonance (NMR) as well as a variety of optical microscopy techniques ranging from single molecule total internal fluorescence (TIRF) microscopy to spectral imaging.

Current laboratory projects include:

i) Monotopic enzymes
ii) Selenoenzymes active site and reaction mechanisms
iii) Membrane deformation by shape controlling proteins