Elucidating the Function of Membrane Proteins using Phospholipid Bilayer Nanodiscs

by Dr. Aditi Das (University of Illinois Urbana-Champaign)

Wednesday, December 21, 2011 from 14:30 to 15:30 (Asia/Kolkata)
at Colaba Campus ( AG-69 )

TIFR, Colaba Mumbai 400005

Description

Membrane proteins, which constitute about 30% of the entire protein content of the cell, are very important pharmaceutical targets. Despite their importance, only a few membrane proteins have been investigated using detailed biophysical techniques. The main barrier to such investigations has been the tendency of membrane proteins to aggregate (due to their hydrophobic nature), in aqueous solution as well as on surfaces. Recently a simple and robust system, called “Nanodisc” has been developed to circumvent the above problem. This system enables the self-assembly of membrane proteins into phospholipid bilayers that mimic the membrane, in a controlled manner. Nanodiscs provide stability and full functionality to a variety of membrane proteins in solution and on surfaces.

This talk will focus on gaining mechanistic understanding of membrane bound cytochrome P450s in Nanodiscs using diverse set of scientific and engineering methodologies. Hepatic cytochrome P450s and in particular cytochrome P450 3A4 (CYP3A4) are membranebound and play a critical role in drug metabolism. The specific direction of this research talk will be on: (1) understanding redox regulation and electron transfer kinetics in human membranebound P450s, which play a critical role in drug metabolism and (2) using ultra-sensitive detection modalities based on localized surface plasmon resonance (LSPR) to monitor membrane protein molecular recognition events. These nanostructures coupled to highly sensitive surface-based detection modalities such as LSPR are used to develop high throughput screening of human therapeutics.