Alpha-helical, but not beta-sheet, propensity of proline is determined by peptide environment.

• DOI: 10.1073/pnas.93.13.6676
• Publication Date: 2002-07-26T14:34:16Z
• Authors: S C Li; N K Goto; K A Williams; C M Deber
• Keywords: Antiparallel (mathematics); Globular protein; Alpha helix; Beta sheet; Helix (gastropod)

Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence Pro residue putative transmembrane helices integral membrane proteins, particularly transport presents structural dilemma. We propose that this phenomenon results from fact propensity given amino acid may be altered to conform changes imposed by molecular environment. To test hypothesis on proline, we synthesized model peptides generic sequence H2N-(Ser-LyS)2-Ala- Leu-Z-Ala-Leu-Z-Trp-Ala-Leu-Z-(Lys-Ser)3-OH (Z = Ala and/or Pro). Peptide conformations were analyzed circular dichroism spectroscopy aqueous buffer, SDS, lysophosphatidylglycerol micelles, organic solvents (methanol, trifluoroethanol, 2-propanol). The helical was found greatly enhanced membrane-mimetic environments lipid micelles solvents. stabilize conformation relative at elevated temperatures 2-propanol, an observation argues against doctrine most alpha-helix media. Parallel studies deoxycholate temperature-induced conformational transitions single-spanning bacteriophage IKe major coat protein, which Pro-containing wild type compared with Pro30 --> mutant, protect helix, but disrupt structure effectively it does water. intrinsic capacity beta-sheets further reflected survey porins where selectively excluded core membrane-spanning barrels. overall data provide rationale for predicting understanding consequences when occurs context membrane.