Putative interaction site for membrane phospholipids controls activation of TRPA1 channel at physiological membrane potentials

Autor: Jonathan Faherty, Sandrine Villette, Sophie Lecomte, Isabel D. Alves, Viktor Sinica, Alexandre Ciaccafava, Lucie Macikova, Viktorie Vlachova, Anna Kadkova
Přispěvatelé: Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Cellular Neurophysiology, Institute of Physiology AS CR, Institute of Physiology [Prague], Czech Academy of Sciences [Prague] (CAS), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), Ciaccafava, Alexandre
Rok vydání: 2019
Předmět:
Phosphatidylinositol 4
5-Diphosphate
0301 basic medicine
[SDV]Life Sciences [q-bio]
Allosteric regulation
[SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Gating
rectification
Biochemistry
Biophysical Phenomena
Protein Structure
Secondary
Membrane Potentials
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
TRP channel
Humans
Inner membrane
Ankyrin
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
peptide-lipid interaction
Lipid bilayer
TRPA1 Cation Channel
Molecular Biology
Phospholipids
ankyrin transient receptor potential
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
Membrane potential
Chemistry
[CHIM.MATE]Chemical Sciences/Material chemistry
Cell Biology
Lipid Metabolism
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Kinetics
HEK293 Cells
030104 developmental biology
Membrane
030220 oncology & carcinogenesis
gating
Biophysics
Calcium
lipids (amino acids
peptides
and proteins)
Peptides
Signal Transduction
Zdroj: Joint 12th EBSA European Biophysics Congress / 10th IUPAP International Conference on Biological Physics (ICBP)
Joint 12th EBSA European Biophysics Congress / 10th IUPAP International Conference on Biological Physics (ICBP), Jul 2019, Madrid, Spain. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 48, pp.S170-S170
FEBS Journal
FEBS Journal, Wiley, 2019, 286 (18), pp.3664-3683. ⟨10.1111/febs.14931⟩
ISSN: 1742-4658
1742-464X
DOI: 10.1111/febs.14931
Popis: International audience; The transient receptor potential ankyrin 1 (TRPA1) channel is a polymodal sensor of environmental irritant compounds, endogenous proalgesic agents, and cold. Upon activation, TRPA1 channels increase cellular calcium levels via direct permeation and trigger signaling pathways that hydrolyze phosphatidylinositol-4,5-bisphosphate (PIP 2) in the inner membrane leaflet. Our objective was to determine the extent to which a putative PIP 2-interaction site (Y1006-Q1031) is involved in TRPA1 regulation. The interactions of two specific peptides (L992-N1008 and T1003-P1034) with model lipid membranes were characterized by biophysical approaches to obtain information about affinity, peptide secondary structure, and peptide effect in the lipid organization. The results indicate that the two peptides interact with lipid membranes only if PIP 2 is present and their affinities depend on the presence of calcium. Using whole-cell electrophysiology, we demonstrate that mutation at F1020 produced channels with faster activation kinetics and with a rightward shifted voltage-dependent activation curve by altering the allosteric constant that couples voltage sensing to pore opening. We assert that the presence of PIP 2 is essential for the interaction of the two peptide sequences with the lipid membrane. The putative phosphoinositide-interacting domain comprising the highly conserved F1020 contributes to the stabilization of the TRPA1 channel gate.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje