Outer membrane protein A of E-coli folds into detergent micelles, but not in the presence of monomeric detergent

Outer membrane protein A (OmpA) of Escherichia coli is a beta-barrel membra ne protein that unfolds in 8 M urea to a random coil, OmpA refolds upon ure a dilution in the presence of certain detergents or lipids. To examine the minimal requirements for secondary and tertiary structure formation in beta -barrel membrane proteins, folding of OmpA was studied as a function of the hydrophobic chain length, the chemical structure of the polar headgroup, a nd the concentration of a large array of amphiphiles. OmpA folded in the pr esence of detergents only above a critical minimal chain length of the apol ar chain as determined by circular dichroism spectroscopy and a SDS-PAGE as say that measures tertiary structure formation. Details of the chemical str ucture of the polar headgroup were unimportant for folding, The minimal cha in length required for folding correlated with the critical micelle concent ration in each detergent series, Therefore, OmpA requires preformed deterge nt micelles for folding and does not adsorb monomeric detergent to its peri meter after folding, Formation of secondary and tertiary structure is therm odynamically coupled and strictly dependent on the interaction with aggrega ted amphiphiles.