The orientations, geometries and lipid interactions of designed transmembrane (TM) peptides have attracted significant experimental and theoretical interest. Because the amino acid proline will introduce a known discontinuity into an alpha-helix, it is important to measure the extent of helix kinking caused by a single proline within an isolated TM helical domain. For this purpose, acetyl-GWWLALALAP10ALALALWWA-ethanolamide was synthesized, and pairs of deuterated alanines were included by using 60-100% deuterated fluorenylmethoxycarbonyl-L-alanine ifmoc-d4-L-Ala) at selected sequence positions. Solid-state deuterium fH) magnetic resonance spectra from oriented, hydrated samples (1140, peptide/lipid; using several lipids) reveal signals from many of the alanine backbone Ca deuterons as well as the alanine side-chain Ca methyl groups, whereas signals from Ca deuterons have not been observed for similar peptides without the proline. It is conceivable that altered peptide dynamics may be responsible for the apparent "unmasking" of the backbone resonances in the presence of the proline. Data analysis based upon the method known as Geometric Analysis of Labeled Alanines ("GALA'') revealed that the peptide helix is significantly distorted due to the presence of the proline. In order to make available valuable additional data points for evaluating the segmental tilt angles of the two halves of the peptide, it may be advisable to substitute selected leucines with d4-alanine. Together the results suggest that the central proline influences not only the geometry but also the dynamics of the membrane-spanning peptide. The results are important for understanding the functional role of proline in several biological families of membrane proteins, including ion channels and others.
Thomas, R. (2009). Influence on Proline Upon the Folding and Geometry of a Model Transmembrane Peptide. Inquiry: The University of Arkansas Undergraduate Research Journal, 10(1). Retrieved from https://scholarworks.uark.edu/inquiry/vol10/iss1/5