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 he determined as a student 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 has since been validated by multiple subsequent studies. The various studies included: a simple cysteine-counting exercise (which showed that hyperthermophilic archaea show a clear abundance of proteins having an even number of cysteine residues), genome-wide sequence-structure mapping calculations (which showed a striking tendency of cysteine residues to be near other cysteine residues in these organisms), and 2D oxidized-reduced SDS gels (which showed an abundance of proteins and protein-complexes held together by disulfide bonds.
The widespread occurrence of disulfide bonds in these organisms helps explain the puzzle of how their proteins are stabilized under such extreme conditions. It also paints a picture of protein disulfide bonding and cellular redox state that is more complex than previously anticipated. Our future efforts aim to exploit the expected presence of disulfide bonds in proteins from these organisms to boost protein structure prediction algorithms.
| Jorda J, Yeates TO
Widespread disulfide bonding in proteins from thermophilic archaea.
Archaea. 2011. 2011:409156. 2011 PMID: 21941460
| Boutz DR, Cascio D, Whitelegge J, Perry LJ, Yeates TO
Discovery of a thermophilic protein complex stabilized by topologically interlinked chains.
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PMC1955483 10.1016/j.jmb.2007.02.078 NIHMS22846
| Beeby M, O’Connor BD, Ryttersgaard C, Boutz DR, Perry LJ, Yeates TO
The genomics of disulfide bonding and protein stabilization in thermophiles.
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| Mallick P, Boutz DR, Eisenberg D, Yeates TO
Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds.
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| Toth EA, Yeates TO
The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway.
Structure. Feb 2000. 8(2):163-74. 2000 PMID: 10673438