SDS micelles as a membrane-mimetic environment for transmembrane segments.

An inherent dilemma in the study of the structural biology of membrane proteins is that it is often necessary to use detergents to mimic the native lipid bilayer environment. This situation is of particular interest because the generation of high-resolution structures (through X-ray crystallography and solution NMR) has overwhelmingly relied upon identification of detergents in which membrane proteins may be solubilized without denaturation into a nonbiological state. While sodium dodecyl sulfate (SDS) is perhaps the most widely employed micelle-forming detergent for laboratory procedures involving membrane proteins, it has generally been regarded as a "harsh" detergent synonymous with membrane protein denaturation. Here we investigate systematically the SDS-solubilized states of a series of model alpha-helical transmembrane (TM) segments of varying Ala and Ile content in conjunction with selected single-Asn polar substitutions. Using Lys-tagged peptides typified by KKKKK-FAIAIAIIAWAIAIIAIAIAI-KKKKK in a series of circular dichroism, fluorescence, TOXCAT dimerization assay, and SDS-PAGE migration experiments, we find that both the local environment of the individual peptide helical surfaces and the formation of oligomeric states within the SDS-peptide complex are highly sensitive to point changes in peptide sequence, particularly with respect to local segment hydrophobicity and polar residue position. The overall results suggest that detergent micelles formed from SDS are largely capable of mimicking the tertiary interactions of protein-, lipid-, and aqueous-exposed helical surfaces that arise in the folded TM domains of proteins. The molecular characteristics of SDS-peptide complexes may thus portend a corresponding role for similar TM sequences in the in vivo assembly of polytopic membrane proteins.