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Structural Bases for the Involvement of Phosphatidylinositol-4,5-bisphosphate in the Internalization of the Cell-Penetrating Peptide Penetratin.
Bechtella, Leïla; Chalouhi, Edward; Milán Rodríguez, Paula; Cosset, Marine; Ravault, Delphine; Illien, Françoise; Sagan, Sandrine; Carlier, Ludovic; Lequin, Olivier; Fuchs, Patrick F J; Sachon, Emmanuelle; Walrant, Astrid.
Afiliación
  • Bechtella L; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Chalouhi E; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Milán Rodríguez P; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Cosset M; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Ravault D; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Illien F; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Sagan S; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Carlier L; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Lequin O; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Fuchs PFJ; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
  • Sachon E; Université de Paris, UFR Sciences du Vivant, 75013 Paris, France.
  • Walrant A; Laboratoire des Biomolécules, LBM, Sorbonne Université, École normale supérieure, PSL University, CNRS, 75005 Paris, France.
ACS Chem Biol ; 17(6): 1427-1439, 2022 06 17.
Article en En | MEDLINE | ID: mdl-35608167
Cell-penetrating peptides cross cell membranes through various parallel internalization pathways. Herein, we analyze the role of the negatively charged lipid phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) in the internalization of Penetratin. Contributions of both inner leaflet and outer leaflet pools of PI(4,5)P2 were revealed by quantifying the internalization of Penetratin in cells treated with PI(4,5)P2 binders. Studies on model systems showed that Penetratin has a strong affinity for PI(4,5)P2 and interacts selectively with this lipid, even in the presence of other negatively charged lipids, as demonstrated by affinity photo-crosslinking experiments. Differential scanning calorimetry experiments showed that Penetratin induces lateral segregation in PI(4,5)P2-containing liposomes, which was confirmed by coarse-grained molecular dynamics simulations. NMR experiments indicated that Penetratin adopts a stabilized helical conformation in the presence of PI(4,5)P2-containing membranes, with an orientation parallel to the bilayer plane, which was also confirmed by all-atom simulations. NMR and photo-crosslinking experiments also suggest a rather shallow insertion of the peptide in the membrane. Put together, our findings suggest that PI(4,5)P2 is a privileged interaction partner for Penetratin and that it plays an important role in Penetratin internalization.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos de Penetración Celular Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Chem Biol Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos de Penetración Celular Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Chem Biol Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos