3.3. Background and Significance 3.3.1. There is a compelling need for novel model membrane media that are optimized for MP structural biology. The vast majority of MP structures determined to date by either NMR or crystallographic methods were determined using classical detergent as the model membrane media. Unfortunately, even mild detergents destabilize MPs relative to their stability in native membranes. Moreover, many of the mildest detergents (such as the alkyl maltoside) routinely fail to yield high quality NMR spectra. More native-like media, such as detergent-lipid mixed micelles or bicelles sometimes offer advantages, but also have drawbacks. Moreover, while membranes from higher organisms almost always contain a considerable mole fraction of cholesterol, very little work has been carried out to establish NMR-compatible media that contain cholesterol, in part because of its very low solubility in detergent solutions. It is clear that there is a need to expand the range of membrane-mimetic media that are available. We propose to design, synthesize (through Core B) and test new surfactants for use in structural biological studies of MPs. We also will test surfactants and cholesterol analogs that have recently been commercialized but not yet well tested.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094608-03
Application #
8379223
Study Section
Special Emphasis Panel (ZGM1-CBB-3)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$421,250
Indirect Cost
$95,958
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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