Protein folding in membranes: insights from neutron diffraction studies of a membrane beta-sheet oligomer.
Studies of the assembly of the hexapeptide Acetyl-Trp-Leu(5) (AcWL(5)) into beta-sheets in membranes have provided insights into membrane protein folding. Yet, the exact structure of the oligomer in the lipid bilayer is unknown. Here we use neutron diffraction to study the disposition of the peptides in bilayers. We find that pairs of adjacent deuterium-labeled leucines have no well-defined peak or dip in the transmembrane distribution profiles, indicative of heterogeneity in the depth of membrane insertion. At the same time, the monomeric homolog AcWL(4) exhibits a homogeneous, well-defined, interfacial location in neutron diffraction experiments. Thus, although the bilayer location of monomeric AcWL(4) is determined by hydrophobicity matching or complementarity within the bilayer, the AcWL(5) molecules in the oligomer are positioned at different depths within the bilayer because they assemble into a staggered transmembrane beta-sheet. The AcWL(5) assembly is dominated by protein-protein interactions rather than hydrophobic complementarity. These results have implications for the structure and folding of proteins in their native membrane environment and highlight the importance of the interplay between hydrophobic complementarity and protein-protein interactions in determining the structure of membrane proteins.
Han
Xue
X
The Johns Hopkins University, Department of Materials Science and Engineering, Baltimore, Maryland 21218, USA.
Hristova
Kalina
K
Wimley
William C
WC
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D033363:Neutron Diffraction; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D014364:Tryptophan; D014867:Water
D008051:Lipid Bilayers; D010455:Peptides; D014867:Water; D014364:Tryptophan