title: PIP2 and Talin Join Forces to Activate Integrin.
abstract: Integrins are major players in cell adhesion and migration, and malfunctions in controlling their activity are associated with various diseases. Nevertheless, the details of integrin activation are not completely understood, and the role of lipids in the process is largely unknown. Herein, we show using atomistic molecular dynamics simulations that the interplay of phosphatidylinositol 4,5-bisphosphate (PIP2) and talin may directly alter the conformation of integrin αIIbβ3. Our results provide a new perspective on the role of PIP2 in integrin activation and indicate that the charged PIP2 lipid headgroup can perturb a clasp at the cytoplasmic face of the integrin heterodimer.
authors: Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
authors: Adam
authors: A
authors: Orłowski
authors: BioMediTech, University of Tampere , FI-33520 Tampere, Finland.|Fimlab Laboratories Ltd. , FI-33520 Tampere, Finland.
authors: Sampo
authors: S
authors: Kukkurainen
authors: Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
authors: Annika
authors: A
authors: Pöyry
authors: Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
authors: Sami
authors: S
authors: Rissanen
authors: Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics and Chemistry, MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark , Campusvej 55, DK-5230 Odense M, Denmark.
authors: Ilpo
authors: I
authors: Vattulainen
authors: BioMediTech, University of Tampere , FI-33520 Tampere, Finland.|Fimlab Laboratories Ltd. , FI-33520 Tampere, Finland.
authors: Vesa P
authors: VP
authors: Hytönen
authors: Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
authors: Tomasz
authors: T
authors: Róg
mesh_terms: D000818:Animals; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry; D051379:Mice; D056004:Molecular Dynamics Simulation; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D016608:Talin / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D019269:Phosphatidylinositol 4,5-Diphosphate; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016608:Talin; C496077:Tln1 protein, mouse