Nate Traaseth Lab

Research

Overview:

Our research is focused on revealing the transport mechanism of membrane proteins through determination of their structure by nuclear magnetic resonance (NMR) spectroscopy. Membrane transport proteins regulate cellular events by acting as gatekeepers of ions, drugs and other essential molecules. Since about half of the drugs on the market target membrane embedded proteins, knowledge of how and why these molecules bind and cause biological activation (or inactivation) is of paramount importance. NMR is particularly well-suited to reveal both the structure and dynamics of these challenging proteins under native membrane conditions without the need for crystallization.

Objectives:

The impact of this research will be to contribute a basic understanding toward how multidrug resistance is conferred to pathogenic organisms on a molecular level.

Research Projects:

(1) Structure Determination of Membrane Proteins within the Small Multidrug Resistance (SMR) Family.

Multidrug resistance is a serious problem in the treatment of infectious diseases. The Institute of Allergy and Infectious Diseases indicates that many diseases are now becoming difficult to treat due to antimicrobial-resistant organisms. Some of these infectious diseases include HIV, tuberculosis, meningitis, staphylococcal infection, influenza, gonorrhea, Candida, and malaria (http://www.cdc.gov/drugresistance/about.html).

Bacteria gain resistance to drugs by a number of mechanisms including: efflux of antibiotics, mutation, permeability of the cell wall, alterations to the antibiotic, changes to the binding sites of antibiotics, or deactivation of the drug molecules. One of the broadest defense mechanisms is through a rather simple mechanism: sending the drug out of the cell. This is the mode of function for the small multidrug resistance (SMR) family of ion-transporter proteins consist of four transmembrane domains and ~110 residues. SMR proteins confer resistance to several quaternary ammonium compounds and other lipophilic cations that are commonly used in spray-fogging procedures for hospital rooms to reduce the number of airborne and surface bacteria.

Nate Traaseth Lab multidrug resistance

Our NMR experiments are aimed at understanding the mechanism of substrate specificity and the ion-coupled transport mechanism


(2) NMR Methodology

Difficult to study biological systems require methodological developments. Due to the difficulty in studying membrane proteins, improvements in both solid-state and solution NMR experiments will make studying membrane proteins more feasible.