Evolution rescues folding of human immunodeficiency virus-1 envelope glycoprotein GP120 lacking a conserved disulfide bond

Rogier W. Sanders, Shang Te D Hsu, Eelco Van Anken, I. Marije Liscaljet, Martijn Dankers, Ilja Bontjer, Aafke Land, Ineke Braakman, Alexandre M J J Bonvin, Ben Berkhout

Research output: Contribution to journalArticlepeer-review

Abstract

The majority of eukaryotic secretory and membrane proteins contain disulfide bonds, which are strongly conserved within protein families because of their crucial role in folding or function. The exact role of these disulfide bonds during folding is unclear. Using virus-driven evolution we generated a viral glycoprotein variant, which is functional despite the lack of an absolutely conserved disulfide bond that links two antiparallel β-strands in a six-stranded β-barrel. Molecular dynamics simulations revealed that improved hydrogen bonding and side chain packing led to stabilization of the β-barrel fold, implying that β-sheet preference codirects glycoprotein folding in vivo. Our results show that the interactions between two β-strands that are important for the formation and/or integrity of the β-barrel can be supported by either a disulfide bond or β-sheet favoring residues.

Original languageEnglish
Pages (from-to)4707-4716
Number of pages10
JournalMolecular Biology of the Cell
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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