title: Residue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance.
abstract: The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH∼6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood. Here, we show the first study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on residue-specific conformation and membrane location describe pHLIP in various surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical membrane-adsorbed state is more complex than previously envisioned. At pH 6.4, for the major unstructured population, the peptide sinks deeper into the membrane in a state II' that is distinct from the adsorbed state II observed at pH 7.4, which may enable pHLIP to sense slight change in acidity even before insertion.
authors.affiliation: Department of Chemistry, State University of New York, Binghamton, New York 13902, USA.
authors.forename: Nicolas S
authors.initials: NS
authors.lastname: Shu
authors.affiliation: Department of Chemistry, State University of New York, Binghamton, New York 13902, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chung
authors.affiliation: Department of Physics, Applied Physics and Astronomy, State University of New York, Binghamton, New York 13902, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Chemistry, State University of New York, Binghamton, New York 13902, USA.
authors.forename: Ming
authors.identifier: 0000000269888058
authors.initials: M
authors.lastname: An
authors.affiliation: Department of Chemistry, State University of New York, Binghamton, New York 13902, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiang
mesh_terms: D006863:Hydrogen-Ion Concentration; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry*; D010713:Phosphatidylcholines
chemical_list: D008565:Membrane Proteins; D010713:Phosphatidylcholines; C533201:pHLIP protein; C028694:1-palmitoyl-2-oleoylphosphatidylcholine