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

Aberle, D.; Muhle-Goll, C. ORCID iD icon 1; Bürck, J. 2; Wolf, M. 3; Reißer, S. 1; Luy, B. ORCID iD icon 1; Wenzel, W. 3; Ulrich, A. S. 1; Meyers, G.
1 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
2 Institut für Biologische Grenzflächen (IBG), Karlsruher Institut für Technologie (KIT)
3 Institut für Nanotechnologie (INT), Karlsruher Institut für Technologie (KIT)


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.

Verlagsausgabe §
DOI: 10.5445/IR/1000049245
Veröffentlicht am 02.03.2018
DOI: 10.1371/journal.ppat.1003973
Zitationen: 30
Web of Science
Zitationen: 30
Zitationen: 31
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Nanotechnologie (INT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2014
Sprache Englisch
Identifikator ISSN: 1553-7366, 1553-7374
KITopen-ID: 1000049245
HGF-Programm 47.02.02 (POF II, LK 01) Synth. biomimetische Werkzeuge IBG 2
Erschienen in PLoS pathogens
Verlag Public Library of Science (PLoS)
Band 10
Heft 2
Seiten Art. Nr.: e1003973
Nachgewiesen in Dimensions
Web of Science
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