This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.113183v1 94/2/492    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Han, X. Articles by Wimley, W. C. Search for Related Content PubMed PubMed Citation Articles by Han, X. Articles by Wimley, W. C.

Protein Folding in Membranes: Insights from Neutron Diffraction Studies of a Membrane β-Sheet Oligomer

Xue Han ^*, Kalina Hristova ^* and William C. Wimley 

^* The Johns Hopkins University, Department of Materials Science and Engineering, Baltimore, Maryland 21218; and Tulane University Health Sciences Center, Department of Biochemistry, New Orleans, Louisiana 70112

Correspondence: Address reprint requests to Kalina Hristova, The Johns Hopkins University, Dept. of Materials Science and Engineering, Baltimore, MD, 21218. Tel.: 410-516-8939; Fax: 410-516-5239; E-mail: kh{at}jhu.edu.

Studies of the assembly of the hexapeptide Acetyl-Trp-Leu₅ (AcWL₅) into β-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 AcWL₄ exhibits a homogeneous, well-defined, interfacial location in neutron diffraction experiments. Thus, although the bilayer location of monomeric AcWL₄ is determined by hydrophobicity matching or complementarity within the bilayer, the AcWL₅ molecules in the oligomer are positioned at different depths within the bilayer because they assemble into a staggered transmembrane β-sheet. The AcWL₅ 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.