CAREER: Controlling Helix-Helix Interactions in Membrane Proteins

Tufts University, Medford MA

Investigators

Abstract

This research program addresses helix-helix interactions in membrane proteins. Materials that phase separate from both aqueous and hydrocarbon solvents will be utilized to direct the packing and assembly of helices within membrane bilayers. Peptides with fluorinated or p-aminophenylalanine residues lining interhelical surfaces and equipped with hydrocarbon sidechains at membrane exposed positions will be used to investigate driving force, packing tendencies, and orientation of the assemblies within the membrane. Using a combination of selected unnatural amino acids, the relationship between sidechain properties and self-assembly will be explored. Biophysical studies detailing the thermodynamics of partitioning and folding will be carried out to obtain a detailed map of peptide-lipid interactions. Sedimentation equilibrium and fluorescence resonance energy transfer in the presence of detergents will be used to ascertain the molecular weight and stoichiometries of the assemblies. Scanning force microscopy will be employed for direct visualization of morphological changes. A variety of curricular changes designed to bring interactivity to the learning environment will be implemented, and a public outreach program in the form of science and policy seminars targeting the non-scientist will be initiated. With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Krishna Kumar, of the Department of Chemistry at Tufts University, is carrying out fundamental studies related to the designed aggregation of proteins. By developing new approaches for the control of how peptide molecules interact with one-another, Professor Kumar's studies may lead to new methods to control the passage of molecules across membranes and to new drug delivery systems. Professor Kumar will bring science to the non-scientist through a public seminar program addressing both science and science policy and will enhance the educational experience of undergraduates through the development of a series of interactive learning projects.