title: Structure of the membrane anchor of pestivirus glycoprotein E(rns), a long tilted amphipathic helix.
abstract: E(rns) is an essential virion glycoprotein with RNase activity that suppresses host cellular innate immune responses upon being partially secreted from the infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a retention/secretion signal. We analyzed the structure and membrane binding properties of this sequence to gain a better understanding of the underlying mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and molecular dynamics simulations confirmed the helical folding and showed that the helix is accommodated in the amphiphilic region of the lipid bilayer with a slight tilt rather than lying parallel to the surface. This model was confirmed by NMR analyses that also identified a central stretch of 15 residues within the helix that is fully shielded from the aqueous layer, which is C-terminally followed by a putative hairpin structure. These findings explain the strong membrane binding of the protein and provide clues to establishing the E(rns) membrane contact, processing and secretion.
authors.affiliation: Institut für Immunologie, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aberle
authors.affiliation: Karlsruhe Institute of Technology, Institut für Organische Chemie, Karlsruhe, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Muhle-Goll
authors.affiliation: Karlsruhe Institute of Technology, Institut für Biologische Grenzflächen (IBG-2), Karlsruhe, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.affiliation: Karlsruhe Institute of Technology, Institut für Nanotechnologie, Karlsruhe, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Karlsruhe Institute of Technology, Institut für Organische Chemie, Karlsruhe, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Reißer
authors.affiliation: Karlsruhe Institute of Technology, Institut für Organische Chemie, Karlsruhe, Germany ; Karlsruhe Institute of Technology, Institut für Biologische Grenzflächen (IBG-2), Karlsruhe, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
authors.affiliation: Karlsruhe Institute of Technology, Institut für Nanotechnologie, Karlsruhe, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wenzel
authors.affiliation: Karlsruhe Institute of Technology, Institut für Organische Chemie, Karlsruhe, Germany ; Karlsruhe Institute of Technology, Institut für Biologische Grenzflächen (IBG-2), Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.affiliation: Institut für Immunologie, Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Meyers
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010576:Pestivirus / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D014759:Viral Envelope Proteins