Date/Time
Date(s) - 05/12/2012
3:20 pm - 4:20 pm

Title: Proteins that Lead to Topological Transitions in Membranes

Speaker: Dr. Gerard Wong

Institute: California NanoSystems Institute – UCLA

Location: ABB 102

Description:

We examine prototypical examples of peptides and proteins that change membrane topology. For example, antimicrobial peptides (AMPs) from innate immunity have broad spectrum antimicrobial activity, and are known to disrupt the barrier function of bacterial membranes specifically, through processes such as pore formation. Using synchrotron small angle x-ray scattering (SAXS), confocal microscopy, and cell based assays, we find that AMPs generate saddle-splay (â??negative Gaussianâ??) membrane curvature, which geometrically enables topological processes such as pore formation, blebbing, and budding selectively in cell membranes. We show why these processes happen in bacterial membranes but not in eukaryotic membranes. Importantly, the need for negative Gaussian curvature places significant constraints on the amino acid composition of all AMPs: The requirement for generating saddle-splay curvature implies that a decrease in arginine content in an AMP can be offset by a simultaneous increase in both lysine and hydrophobic content. This rule is consistent with the amino acid compositions of 1,080 known cationic AMPâ??s, and can inform current approaches to develop new antimicrobials. In addition to antimicrobial peptides, we will also describe two cognate systems from the same perspective: cell penetrating peptides (CPPs), and apoptosis proteins of the Bcl2 family. By using 3rd generation synchrotrons to measure the density propagator of water, we show that it is possible to make movies of hydration structure and dynamics at femtosecond timescales and sub-Angstrom lengthscales. We use this Greens function method to explore water dynamics in confined geometries, such as those in 1-D pores and 2-D channels.