ENHANCED CELL TOLERANCE AND SURVIVAL IN EXTREME ENVIRONMENTS: ELUCIDATING THE ROLE OF ARCHAEAL MOLECULAR CHAPERONES
Abstract
Molecular chaperones assist non-native proteins reach their correct conformations by preventing protein aggregation or providing an appropriate environment for protein folding. Chaperones are particularly important in extremophiles that must tolerate extremes of temperature, pressure, or salinity. One family of archaeal chaperones are the prefoldins (PFDs), which arrest protein misfolding and aggregation, transferring unfolded proteins to other chaperones for refolding. The PFDs are generally hexameric complexes consisting of two ? and four ? subunits in a jellyfish-like assembly. However, a PFD variant called gamma-prefoldin (gammaPFD), isolated from the deep-sea hyperthermophile Methanocaldococcus jannaschii, exhibits a unique filamentous structure comprising hundreds of monomeric subunits. Although the gammaPFD is structurally homologous to ?PFD, it does not interact with either ?- or ?PFD subunits, and the functional reasons and advantages for a filamentous assembly are unclear. Potential roles of the filament include stabilizing cellular membrane components and/or arresting protein aggregation as the cells undergo heat shock. Furthermore, filamentous PFDs may have a general role in the survival of hyperthermophiles at extreme temperatures. Bioinformatics suggest a variety of hyperthermophiles produce filamentous PFDs, although no other filaments have yet been isolated and characterized. We will investigate the mechanistic function of filamentous PFDs by manipulating their expression and assembly within M. jannaschii, enabled by recently developed genetic tools for methanogens. The thermotolerance and cellular morphology conferred by filamentous gammaPFD will be examined in response to heat shock, including specific interactions between filaments and subcellular components. We will also screen for filamentous PFDs originating from other hyperthermophilic species, and investigate how these variants function when expressed in M. jannaschii lacking native gammaPFD.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2021
- Source ID
- FA95502010389
Entities
People
- Douglas S Clark
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of California Regents