Methods to study membrane protein structure in solution

Membrane protein structure is difficult to determine by any technique. NMR spectroscopy of membrane proteins in solution can proceed using methods identical to those that have been successfully applied to numerous water-soluble proteins providing suitable solubilization conditions can be found. Organic solvents and small detergent micelles have correlation times short enough for structure determination based on 1H NOEs. Although it is difficult to generalize as each system is unique, organic solvents and micelles of strong detergents such as SDS are useful for amphiphilic peptides and small membrane proteins, whereas larger proteins need milder treatment to preserve the tertiary structure. Small unilamellar phospholipid vesicles are much too large for NOE-based structure determination, but they still fall under the domain of solution-state NMR and can be useful in certain circumstances.