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Title: Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1–E2 disulfide bondmore » formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.« less
Authors:
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Publication Date:
OSTI Identifier:
22435026
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 454-455; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 60 APPLIED LIFE SCIENCES; ANCHORS; ARGININE; ATOMIC MODELS; BONDING; CRYSTAL STRUCTURE; DISULFIDES; GEOMETRY; GLYCOPROTEINS; HISTIDINE; LIMITING VALUES; MEMBRANE PROTEINS; MEMBRANES; PH VALUE; SENSORS; STRUCTURAL MODELS