Structure of the Membrane Anchor of Pestivirus Glycoprotein Erns, a Long Tilted Amphipathic Helix

PLoS Pathogens

Daniel Aberle¹  Wolfgang Wenzel²  Jochen Bürck²  Moritz Wolf³  Anne S. Ulrich³  Claudia Muhle-Goll⁴  Sabine Reißer⁴  Burkhard Luy⁴  Gregor Meyers⁴ 

[1] Institut für Immunologie, Friedrich-Loeffler-Institut, Greifswald – Insel Riems, Germany;Karlsruhe Institute of Technology, Institut für Biologische Grenzflächen (IBG-2), Karlsruhe, Germany;Karlsruhe Institute of Technology, Institut für Nanotechnologie, Karlsruhe, Germany;Karlsruhe Institute of Technology, Institut für Organische Chemie, Karlsruhe, Germany

关键词: Protons;    Monte Carlo method;    Integral membrane proteins;    Protein structure;    Proteases;    Lipids;    Ribonucleases;    Vesicles;   

DOI  :  10.1371/journal.ppat.1003973

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Erns 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 Erns membrane contact, processing and secretion.

【 授权许可】

CC BY