title: Membrane association of the PTEN tumor suppressor: neutron scattering and MD simulations reveal the structure of protein-membrane complexes.
abstract: Neutron reflection (NR) from planar interfaces is an emerging technology that provides unique and otherwise inaccessible structural information on disordered molecular systems such as membrane proteins associated with fluid bilayers, thus addressing one of the remaining challenges of structural biology. Although intrinsically a low-resolution technique, using structural information from crystallography or NMR allows the construction of NR models that describe the architecture of protein-membrane complexes at high resolution. In addition, a combination of these methods with molecular dynamics (MD) simulations has the potential to reveal the dynamics of protein interactions with the bilayer in atomistic detail. We review recent advances in this area by discussing the application of these techniques to the complex formed by the PTEN phosphatase with the plasma membrane. These studies provide insights in the cellular regulation of PTEN, its interaction with PI(4,5)P2 in the inner plasma membrane and the pathway by which its substrate, PI(3,4,5)P3, accesses the PTEN catalytic site.
authors.affiliation: Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA; NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Hirsh
authors.initials: H
authors.lastname: Nanda
authors.affiliation: Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA; NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinrich
authors.affiliation: Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. Electronic address: quench@cmu.edu.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lösche
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction / Q000379:methods*; D051059:PTEN Phosphohydrolase / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Molecular dynamics simulations; Neutron reflection; PTEN; Phosphatidylinositolphosphate; Phosphatidylserine; Protein–membrane complex; Tethered bilayer lipid membranes