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  • 标题:Kinetics of pHLIP peptide insertion into and exit from a membrane
  • 本地全文:下载
  • 作者:Gregory Slaybaugh ; Dhammika Weerakkody ; Donald M. Engelman
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2020
  • 卷号:117
  • 期号:22
  • 页码:12095-12100
  • DOI:10.1073/pnas.1917857117
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:To advance mechanistic understanding of membrane-associated peptide folding and insertion, we have studied the kinetics of three single tryptophan pHLIP (pH-Low Insertion Peptide) variants, where tryptophan residues are located near the N terminus, near the middle, and near the inserting C-terminal end of the pHLIP transmembrane helix. Single-tryptophan pHLIP variants allowed us to probe different parts of the peptide in the pathways of peptide insertion into the lipid bilayer (triggered by a pH drop) and peptide exit from the bilayer (triggered by a rise in pH). By using pH jumps of different magnitudes, we slowed down the processes and established the intermediates that helped us to understand the principles of insertion and exit. The obtained results should also aid the applications in medicine that are now entering the clinic.
  • 关键词:membrane-associated folding ; tumor acidity ; fluorescence ; kinetics ; pHLIP
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