{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:11:46Z","timestamp":1793427106439,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,6,25]]},"abstract":"<jats:p>Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence of the Pro residue in the putative transmembrane helices of integral membrane proteins, particularly transport proteins, presents a structural dilemma. We propose that this phenomenon results from the fact that the structural propensity of a given amino acid may be altered to conform to changes imposed by molecular environment. To test this hypothesis on proline, we synthesized model peptides of 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 by circular dichroism spectroscopy in aqueous buffer, SDS, lysophosphatidylglycerol micelles, and organic solvents (methanol, trifluoroethanol, and 2-propanol). The helical propensity of Pro was found to be greatly enhanced in the membrane-mimetic environments of both lipid micelles and organic solvents. Proline was found to stabilize the alpha-helical conformation relative to Ala at elevated temperatures in 2-propanol, an observation that argues against the doctrine that Pro is the most potent alpha-helix breaker as established in aqueous media. Parallel studies in deoxycholate micelles of the temperature-induced conformational transitions of the single-spanning membrane bacteriophage IKe major coat protein, in which the Pro-containing wild type was compared with Pro30 --&gt; Ala mutant, Pro was found to protect the helix, but disrupt the beta-sheet structure as effectively as it does to model peptides in water. The intrinsic capacity of Pro to disrupt beta-sheets was further reflected in a survey of porins where Pro was found to be selectively excluded from the core of membrane-spanning beta-sheet barrels. The overall data provide a rationale for predicting and understanding the structural consequences when Pro occurs in the context of a membrane.<\/jats:p>","DOI":"10.1073\/pnas.93.13.6676","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"6676-6681","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":303,"title":["Alpha-helical, but not beta-sheet, propensity of proline is determined by peptide environment."],"prefix":"10.1073","volume":"93","author":[{"given":"S C","family":"Li","sequence":"first","affiliation":[{"name":"Division of Biochemistry Research, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N K","family":"Goto","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Research, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K A","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Research, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Deber","sequence":"additional","affiliation":[{"name":"Division of Biochemistry Research, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,6,25]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.13.6676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:22:01Z","timestamp":1649863321000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.13.6676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,6,25]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1996,6,25]]}},"alternative-id":["10.1073\/pnas.93.13.6676"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.13.6676","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,6,25]]},"assertion":[{"value":"1996-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}