The negative charge of the membrane has opposite effects on the membrane entry and exit of pH-low insertion peptide

Biochemistry. 2015 Mar 10;54(9):1709-12. doi: 10.1021/acs.biochem.5b00069. Epub 2015 Feb 27.

Abstract

The pH-low insertion peptide (pHLIP) targets acidic diseases such as cancer. The acidity of the environment causes key aspartic acids in pHLIP to become protonated, causing the peptide to insert into membranes. Here we investigate how the negative charge of the membrane influences how pHLIP enters and exits the lipid bilayer. We found that electrostatic repulsion affected differently the membrane entry and exit of pHLIP for negatively charged membranes. As a consequence, a large hysteresis was observed. We propose this is not a consequence of structural changes but results from local changes in the environment of aspartic acids, shifting their pK values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism*
  • Electric Conductivity
  • Electrons
  • Humans
  • Hydrogen-Ion Concentration
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Protein Transport

Substances

  • Lipid Bilayers
  • Membrane Proteins
  • pHLIP protein