Peptide conformational changes induced by tryptophan-phosphocholine interactions in a micelle.
Sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC) micelles are often used to mimic the membrane- or receptor-bound states of peptides in NMR studies. From the present examination of a 26-residue analog of exendin-4 (TrEX4) by NMR and CD in water, aqueous 30% trifluoroethanol (TFE), and bound to both SDS and DPC micelles, it is clear that these two lipid micelles can yield very different peptide structures. The Trp-cage fold (also observed in 30% TFE) is present when TrEX4 is bound to SDS micelles; however, tertiary structure is absent in the presence of DPC micelles. The loss of tertiary structure is attributed to an energetically favorable interaction (estimated as 2-3 kcal/mol) of the tryptophan side chain with the phosphocholine head groups. These dramatic structural differences suggest that care must be taken when using either SDS or DPC to mimic the membrane- or receptor-bound states.
Neidigh
Jonathan W
JW
Department of Chemistry, University of Washington, Seattle 98195, USA.
Andersen
Niels H
NH
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D000077270:Exenatide; D066298:In Vitro Techniques; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D010767:Phosphorylcholine / Q000737:chemistry; D011487:Protein Conformation; D012996:Solutions; D014364:Tryptophan / Q000737:chemistry*; D014688:Venoms
D008823:Micelles; D010455:Peptides; D012996:Solutions; D014688:Venoms; D010767:Phosphorylcholine; D014364:Tryptophan; D000077270:Exenatide