“Hot” Protein and the Iron Paradox

Iron, one of earth’s most abundant elements, plays a paradoxical role in biology.  On the one hand, iron is an essential element for nearly all of life, but on the other hand it is universally toxic. Iron is necessary in our cells because it helps with electron shuttling, which is essential to produce ATP, the universal “fuel” for all life. Not surprisingly, the toxicity of iron is also coupled to this electron shuttling.  In the presence of oxygen, ferrous iron (Fe2+) readily generates reactive oxygen species (ROS) that cause oxidative stress, which is dangerous to the cell. A research group under the direction of TBI scientist Trevor Douglas, in collaboration with TBI’s Mark Young, has recently identified, isolated, and characterized an antioxidant protein from the thermoacidophilic archaeon, Sulfolobus solfataricus (SsDPSL). This protein manages the “iron paradox” by using the electron shuttling properties of iron to benefit the cell while also protecting the cell from oxidative stress. Their results were featured on the cover of the Proceedings of the National Academy of Sciences.

Biochemical characterization indicated that this paradox-solving protein was both structurally and functionally related to a previously characterized class of DNA binding proteins isolated from nutrient starved cells. Although biochemically similar to previously described DPS proteins, further analysis of this sequence revealed a new monophyletic subclass of proteins that are related but not identical to previously characterized DPS proteins.  Based on structural and functional similarities between this Sulfolobus protein and previously described DPS proteins, this new sub-class of proteins was named  “Dps-like” (DPSL).   While the phylogenetic distinction between these proteins subclasses is well supported, Douglas has established a collaboration with TBI structural biologist Dr. Martin Lawrence in an effort to identify the structural distinctions between DPS proteins and their relatives, DPSL proteins. 

Looking forward, the Douglas team has used the ssdpsl gene, which codes for the DPSL protein, as an indicator of oxidative stress in Sulfolobus and have assembled an international team, which includes local collaborators, Drs. Bothner, Lawrence and Young from the Thermal Biology Institute, to study the cellular response of Sulfolobus to oxidative and other stresses.

These findings were featured on the cover of the July 2005 issue of PNAS.