title: Dynamic interactions between a membrane binding protein and lipids induce fluctuating diffusivity.
abstract: Pleckstrin homology (PH) domains are membrane-binding lipid recognition proteins that interact with phosphatidylinositol phosphate (PIP) molecules in eukaryotic cell membranes. Diffusion of PH domains plays a critical role in biological reactions on membrane surfaces. Although diffusivity can be estimated by long-time measurements, it lacks information on the short-time diffusive nature. We reveal two diffusive properties of a PH domain bound to the surface of a PIP-containing membrane using molecular dynamics simulations. One is fractional Brownian motion, attributed to the motion of the lipids with which the PH domain interacts. The other is temporally fluctuating diffusivity; that is, the short-time diffusivity of the bound protein changes substantially with time. Moreover, the diffusivity for short-time measurements is intrinsically different from that for long-time measurements. This fluctuating diffusivity results from dynamic changes in interactions between the PH domain and PIP molecules. Our results provide evidence that the complexity of protein-lipid interactions plays a crucial role in the diffusion of proteins on biological membrane surfaces. Changes in the diffusivity of PH domains and related membrane-bound proteins may in turn contribute to the formation/dissolution of protein complexes in membranes.
authors.affiliation: Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Leeds Institute of Cancer and Pathology, School of Medicine, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, UK.
authors.forename: Antreas C
authors.initials: AC
authors.lastname: Kalli
authors.affiliation: Department of Mechanical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 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, UK.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D000072417:Protein Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C486555:DAPP1 protein, human; D008563:Membrane Lipids; D008565:Membrane Proteins
keywords: Anomalous diffusion; Molecular dynamics simulations; Peripheral membrane proteins; Phosphatidyl-inositol-phosphate; Pleckstrin homology domains