title: Interaction of a peptide derived from C-terminus of human TRPA1 channel with model membranes mimicking the inner leaflet of the plasma membrane.
abstract: 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.
authors: CBMN-UMR 5248 CNRS, University of Bordeaux, IPB, Allée Geoffroy St. Hilaire, 33600 Pessac, France; Department of Cellular Neurophysiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
authors: Katja
authors: K
authors: Witschas
authors: CBMN-UMR 5248 CNRS, University of Bordeaux, IPB, Allée Geoffroy St. Hilaire, 33600 Pessac, France.
authors: Marie-Lise
authors: ML
authors: Jobin
authors: INSERM, U869, ARNA Laboratory, University of Bordeaux, 2 rue Robert Escarpit, 33607 Pessac, France.
authors: Dursun Nizam
authors: DN
authors: Korkut
authors: CBMN-UMR 5248 CNRS, University of Bordeaux, IPB, Allée Geoffroy St. Hilaire, 33600 Pessac, France.
authors: Maria Magdalena
authors: MM
authors: Vladan
authors: INSERM, U869, ARNA Laboratory, University of Bordeaux, 2 rue Robert Escarpit, 33607 Pessac, France.
authors: Gilmar
authors: G
authors: Salgado
authors: CBMN-UMR 5248 CNRS, University of Bordeaux, IPB, Allée Geoffroy St. Hilaire, 33600 Pessac, France.
authors: Sophie
authors: S
authors: Lecomte
authors: Department of Cellular Neurophysiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
authors: Viktorie
authors: V
authors: Vlachova
authors: CBMN-UMR 5248 CNRS, University of Bordeaux, IPB, Allée Geoffroy St. Hilaire, 33600 Pessac, France. Electronic address: i.alves@cbmn.u-bordeaux.fr.
authors: Isabel D
authors: ID
authors: Alves
mesh_terms: D016880:Anisotropy; D002021:Buffers; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008567:Membranes, Artificial; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D044367:Phase Transition; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002021:Buffers; D015220:Calcium Channels; D008563:Membrane Lipids; D008567:Membranes, Artificial; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
keywords: Conformation; Lipid-selective interaction; Peptide–lipid interactions; Secondary structure; TRP channels