title: Anomalous behavior of water inside the SecY translocon.
abstract: The heterotrimeric SecY translocon complex is required for the cotranslational assembly of membrane proteins in bacteria and archaea. The insertion of transmembrane (TM) segments during nascent-chain passage through the translocon is generally viewed as a simple partitioning process between the water-filled translocon and membrane lipid bilayer, suggesting that partitioning is driven by the hydrophobic effect. Indeed, the apparent free energy of partitioning of unnatural aliphatic amino acids on TM segments is proportional to accessible surface area, which is a hallmark of the hydrophobic effect [Öjemalm K, et al. (2011) Proc Natl Acad Sci USA 108(31):E359-E364]. However, the apparent partitioning solvation parameter is less than one-half the value expected for simple bulk partitioning, suggesting that the water in the translocon departs from bulk behavior. To examine the state of water in a SecY translocon complex embedded in a lipid bilayer, we carried out all-atom molecular-dynamics simulations of the Pyrococcus furiosus SecYE, which was determined to be in a "primed" open state [Egea PF, Stroud RM (2010) Proc Natl Acad Sci USA 107(40):17182-17187]. Remarkably, SecYE remained in this state throughout our 450-ns simulation. Water molecules within SecY exhibited anomalous diffusion, had highly retarded rotational dynamics, and aligned their dipoles along the SecY transmembrane axis. The translocon is therefore not a simple water-filled pore, which raises the question of how anomalous water behavior affects the mechanism of translocon function and, more generally, the partitioning of hydrophobic molecules. Because large water-filled cavities are found in many membrane proteins, our findings may have broader implications.
authors.affiliation: Department of Physiology and Biophysics and Center for Biomembrane Systems, University of California, Irvine, CA 92697-4560;
authors.forename: Sara
authors.initials: S
authors.lastname: Capponi
authors.affiliation: Department of Chemistry and Center for Biomembrane Systems, University of California, Irvine, CA 92697-2025;
authors.forename: Matthias
authors.initials: M
authors.lastname: Heyden
authors.affiliation: Theoretical Molecular Biophysics, Department of Physics, Freie Universität Berlin, D-14195 Berlin-Dahlem, Germany.
authors.forename: Ana-Nicoleta
authors.initials: AN
authors.lastname: Bondar
authors.affiliation: Department of Chemistry and Center for Biomembrane Systems, University of California, Irvine, CA 92697-2025;
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Tobias
authors.affiliation: Department of Physiology and Biophysics and Center for Biomembrane Systems, University of California, Irvine, CA 92697-4560; stephen.white@uci.edu.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: White
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D020027:Pyrococcus furiosus / Q000378:metabolism*; D055672:Static Electricity; D014867:Water / Q000737:chemistry*
chemical_list: D019843:Archaeal Proteins; D008051:Lipid Bilayers; D014867:Water
keywords: confined water; membrane protein folding; molecular dynamics; protein hydration; protein-conducting channel