The Disulfide Bonds within BST-2 Enhance Tensile Strength during Viral Tethering

Biochemistry
Kelly E Du PontChristopher E Berndsen

Abstract

Human BST-2/tetherin is a host factor that inhibits the release of enveloped viruses, including HIV-1, HIV-2, and SIV, from the cell surface by tethering viruses to the host cell membrane. BST-2 has an α-helical ectodomain that forms disulfide-linked dimers between two monomers forming a coiled coil. The ectodomain contains three cysteine residues that can participate in disulfide bond formation and are critical for viral tethering. The role of the disulfides in viral tethering is unknown but proposed to be for maintaining the dimer. We explored the role of the disulfides in the structure of BST-2 using experimental, biophysical methods. To understand the role of the disulfides in viral tethering, we used a new approach in viral tethering, steered molecular dynamics. We find that the disulfides coordinate the unfolding of the BST-2 monomers, which adds tensile strength to the coiled coil. Structural differences between oxidized and reduced BST-2 are apparent during unfolding, showing the monomers slide past each other in the absence of the disulfides. We found no evidence to support dissociation of the dimer upon reduction of the disulfide bonds. Moreover, the structure of BST-2 in the absence of the disulfides is similar to th...Continue Reading

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Citations

Aug 6, 2017·Proteins·Kadir A Ozcan, Christopher E Berndsen
Jan 23, 2019·Protein Science : a Publication of the Protein Society·Jacob A WhitleyNathan T Wright
Jun 12, 2019·PeerJ·Ian R RoyChristopher E Berndsen

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