Todd Yeates
Disulfide-rich Thermophiles
The cytosolic environment of most well-studied organisms is chemically reducing. As a result, stabilizing disulfide bonds are generally absent from cytosolic proteins, though they are abundant in extracellular proteins, including those that are secreted and those that reside in the bacterial periplasmic space. However, this simplistic textbook view of protein disulfide bonding is apparently violated by certain organisms. Based upon a crystal structure of a hyperthermophilic protein determined in 2000, Eric Toth predicted that certain thermophiles are able to use disulfide bonding to stabilize their proteins against extreme conditions. This claim was supported by Parag Mallick in 2002 using computational approaches, and by multiple lines of experimental evidence by Morgan Beeby et al. in 2005 and Danny Boutz in 2007. One archaeon in which the phenomenon has now been firmly established is Pyrobaculum aerophilum. Recent data from other groups are beginning to paint a picture of cellular protein disulfide bonding that is more complex than was once thought.
References:
- Toth, E.A., Worby, C., Dixon, J.E., Goedken, E.R., Marqusee, S., and Yeates, T.O. 2000. The Crystal Structure of Adenylosuccinate Lyase from Pyrobaculum aerophilum Reveals an Intracellular Protein with Three Disulfide Bonds. J. Mol. Biol., 301, 433-450.
- Mallick, P., Boutz, D.R., Eisenberg, D., and Yeates, T.O. 2002. Genomic Evidence that the Intracellular Proteins of Archaeal Microbes Contain Disulfide Bonds. Proc. Natl. Acad. Sci. USA 99, 9679-9684.
- Beeby, M., O'connor, B.D., Ryttersgaard, C., Boutz, D.R., Perry, L.J., Yeates, T.O. 2005. The Genomics of Disulfide Bonding and Protein Stabilization in Thermophiles. PLoS Biol. 3, PLoS Biol. 3, 1549-58.
- Boutz, D.R., Cascio, D., Whitelegge, J., Perry, L.J., and Yeates, T.O. (2007). Discovery of a thermophilic protein complex stabilized by topologically interlinked chains. J. Mol. Biol. 368, 1332-44.
