title: Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA. Electronic address: jimin.wang@yale.edu.
authors.forename: Jimin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA. Electronic address: yorgo.modis@yale.edu.
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
mesh_terms: D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D010576:Pestivirus / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D014759:Viral Envelope Proteins
keywords: Amphipathic helix; Arginine snorkel; Histidine pH sensor; Membrane anchor; Membrane fusion protein; Secondary structure prediction; Transmembrane helix; Type I membrane protein
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