title: Anomalous Dynamics of a Lipid Recognition Protein on a Membrane Surface.
abstract: Pleckstrin homology (PH) domains are lipid-binding modules present in peripheral membrane proteins which interact with phosphatidyl-inositol phosphates (PIPs) in cell membranes. We use multiscale molecular dynamics simulations to characterize the localization and anomalous dynamics of the DAPP1 PH domain on the surface of a PIP-containing lipid bilayer. Both translational and rotational diffusion of the PH domain on the lipid membrane surface exhibit transient subdiffusion, with an exponent α ≈ 0.5 for times of less than 10 ns. In addition to a PIP3 molecule at the canonical binding site of the PH domain, we observe additional PIP molecules in contact with the protein. Fluctuations in the number of PIPs associated with the PH domain exhibit 1/f noise. We suggest that the anomalous diffusion and long-term correlated interaction of the PH domain with the membrane may contribute to an enhanced probability of encounter with target complexes on cell membrane surfaces.
authors.affiliation: Department of Mechanical Engineering, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
authors.forename: Antreas C
authors.initials: AC
authors.lastname: Kalli
authors.affiliation: Department of Mechanical Engineering, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Department of Mechanical Engineering, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasuoka
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D000465:Algorithms; D002462:Cell Membrane / Q000378:metabolism*; D008051:Lipid Bilayers; D058635:Lipid-Linked Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs
chemical_list: D008051:Lipid Bilayers; D058635:Lipid-Linked Proteins; D018129:Phosphatidylinositol Phosphates