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Structural Mechanism of Viral Tethering by the Anti‐Viral Protein BST‐2
Author(s) -
Ozcan Kadir,
Berndsen Christopher
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.630.3
Subject(s) - tetherin , viral envelope , microbiology and biotechnology , transmembrane protein , chemistry , membrane , transmembrane domain , budding , biophysics , viral protein , cell membrane , biology , biochemistry , virus , glycoprotein , virology , receptor
BST‐2/tetherin is a human extracellular transmembrane protein that serves as a host defense factor against HIV‐1, HIV‐2, SIV, and other viruses by inhibiting viral budding. Structurally, BST‐2 is a homo‐dimeric coiled‐coil that is connected to the host cell membrane by N and C terminal transmembrane anchors. The coiled‐coil structure of BST‐2 is strengthened by three disulfide bonds between cysteine residues of the monomers. The structural mechanism of viral budding and tethering as mediated by BST‐2 is not clear. In order to describe the mechanism of viral tethering, we created a physiologically relevant model of BST‐2 embedded in a membrane. We also post‐translationally modified the BST‐2 with glycosylation at the known sites and equilibrated the model to create a stable structure of membrane associated BST‐2. Through steered molecular dynamics, viral tethering was simulated to illustrate the structural transitions in BST‐2 between the host cell membrane associated BST‐2 and the cell‐virus membrane bridging form. We find that the membrane and disulfides did not affect the structural transitions of BST‐2. Regardless of the disulfides, glycosylation, or presence of the membrane, BST‐2 consistently unwound at non‐ideal heptads. Therefore, sequence encoded weaknesses in the BST‐2 coiled‐coil region allow for a smooth transition between the host cell membrane associated BST‐2 and cell‐virus membrane bridging form. Support or Funding Information NSF‐REU award CHE‐1461175 the 4‐VA organization