title: The negative charge of the membrane has opposite effects on the membrane entry and exit of pH-low insertion peptide.
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.
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Haden L
authors.initials: HL
authors.lastname: Scott
authors.forename: Vanessa P
authors.initials: VP
authors.lastname: Nguyen
authors.forename: Daiane S
authors.initials: DS
authors.lastname: Alves
authors.forename: Forrest L
authors.initials: FL
authors.lastname: Davis
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Booth
authors.forename: Jordan
authors.initials: J
authors.lastname: Bryner
authors.forename: Francisco N
authors.initials: FN
authors.lastname: Barrera
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D004553:Electric Conductivity; D004583:Electrons; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; C533201:pHLIP protein