TY - JOUR
T1 - Evolution rescues folding of human immunodeficiency virus-1 envelope glycoprotein GP120 lacking a conserved disulfide bond
AU - Sanders, Rogier W.
AU - Hsu, Shang Te D
AU - Van Anken, Eelco
AU - Marije Liscaljet, I.
AU - Dankers, Martijn
AU - Bontjer, Ilja
AU - Land, Aafke
AU - Braakman, Ineke
AU - Bonvin, Alexandre M J J
AU - Berkhout, Ben
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E08-07-0670
DO - 10.1091/mbc.E08-07-0670
M3 - Article
C2 - 18753405
AN - SCOPUS:58149288655
VL - 19
SP - 4707
EP - 4716
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 11
ER -