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The transient receptor potential ankyrin 1 channel (TRPA1) belongs to the TRP cation channel superfamily that responds to a panoply of stimuli such as changes in temperature, calcium levels, reactive oxygen and nitrogen species and lipid mediators among others. The TRP superfamily has been implicated in diverse pathological states including neurodegenerative disorders, kidney diseases, inflammation, pain and cancer. The intracellular C-terminus is an important regulator of TRP channel activity. Studies with this and other TRP superfamily members have shown that the C-terminus association with lipid bilayer alters channel sensitivity and activation, especially interactions occurring through basic residues. Nevertheless, it is not yet clear how this process takes place and which regions in the C-terminus would be responsible for such membrane recognition. With that in mind, herein the first putative membrane interacting region of the C-terminus of human TRPA1, (corresponding to a 29 residue peptide, IAEVQKHASLKRIAMQVELHTSLEKKLPL) named H1 due to its potential helical character was chosen for studies of membrane interaction. The affinity of H1 to lipid membranes, H1 structural changes occurring upon this interaction as well as effects of this interaction in lipid organization and integrity were investigated using a biophysical approach. Lipid models systems composed of zwitterionic and anionic lipids, namely those present in the lipid membrane inner leaflet, where H1 is prone to interact, where used. The study reveals a strong interaction and affinity of H1 as well as peptide structuration especially with membranes containing anionic lipids. Moreover, the interactions and peptide structure adoption are headgroup specific.

Original publication

DOI

10.1016/j.bbamem.2015.02.003

Type

Journal article

Journal

Biochim Biophys Acta

Publication Date

05/2015

Volume

1848

Pages

1147 - 1156

Keywords

Conformation, Lipid-selective interaction, Peptide–lipid interactions, Secondary structure, TRP channels, Anisotropy, Buffers, Calcium Channels, Cell Membrane, Humans, Hydrogen-Ion Concentration, Membrane Lipids, Membranes, Artificial, Nerve Tissue Proteins, Nuclear Magnetic Resonance, Biomolecular, Peptide Fragments, Phase Transition, Protein Binding, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Structure-Activity Relationship, Transient Receptor Potential Channels