Evolution rescues folding of human immunodeficiency virus-1 envelope glycoprotein GP120 lacking a conserved disulfide bond.
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 beta-strands in a six-stranded beta-barrel. Molecular dynamics simulations revealed that improved hydrogen bonding and side chain packing led to stabilization of the beta-barrel fold, implying that beta-sheet preference codirects glycoprotein folding in vivo. Our results show that the interactions between two beta-strands that are important for the formation and/or integrity of the beta-barrel can be supported by either a disulfide bond or beta-sheet favoring residues.
Sanders
Rogier W
RW
Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. r.w.sanders@amc.uva.nl
Hsu
Shang-Te D
ST
van Anken
Eelco
E
Liscaljet
I Marije
IM
Dankers
Martijn
M
Bontjer
Ilja
I
Land
Aafke
A
Braakman
Ineke
I
Bonvin
Alexandre M J J
AM
Berkhout
Ben
B