Hsp70 molecular chaperones in the cell

My research is primarily focused on understanding the mechanisms underlying protein folding in the eukaryotic cell. Hence, how the cell maintains proper protein folding capacity to avoid disease states caused by misfolded proteins. This protein homeostasis, or proteostasis, is based on the expression of specialized molecular chaperones that aid in protein folding by binding the unfolded protein clients and helping them to fold.

Hsp70 chaperones are abundant cellular factors that play essential roles in many important processes by facilitating protein folding or conformational transitions. Presently, research efforts have defined the biochemical core activity of the Hsp70, determined that this chaperone is essential for cellular functions and defined a network of interacting factors that modulate its function. However, currently we lack an understanding of the in vivo functions of Hsp70 and how this general chaperone is recruited to specific folding clients within the cell.

Specifically, I’m interested in understanding how the Hsp70 chaperone activity is allocated within the eukaryotic cell. Likely, the cellular network of Hsp70 interacting proteins plays a key role in targeting the Hsp70 to its various folding substrates. My focus is on a class of cofactors called Nucleotide Exchange Factors (NEFs). The recent identification of three main classes of NEFs present in the cytoplasm of all eukaryotic cells suggests that they have specific functions. Hence, they would be ideally suited to act as specificity factors that allocate the Hsp70 activity in the cell. In the light of the recently developed strategies to combat disease by restoring cellular proteostasis, NEF-defined cellular functions of Hsp70 might present viable targets for pharmacological intervention.

Currently, my group is investigating the in vivo role of the cytoplasmic NEFs in the model eukaryote yeast (Saccharomyces cerevisiae), by applying a combination of cell biological and genetic techniques.

During autumn 2010, I’m recruiting students for the group. Projects are already up running and benefit from the strong research environment at the Wenner-Gren Institute that also harbors several yeast labs.

Selected publications:

Andréasson C., Fiaux J., Rampelt H., and Bukau B. (2010) The endoplasmic reticulum Grp170 acts as a nucleotide exchange factor of Hsp70 via a mechanism similar to that of the cytosolic Hsp110 J Biol Chem. 285:12445-53.

Andréasson C., Fiaux J., Rampelt H., Druffel S. and Bukau B. (2008) Insights into the structural dynamics of the Hsp110-Hsp70 interaction reveal the mechanism for nucleotide exchange activity Proc Nat Acad Sci. 105:16519-24

Sadlish H., Rampelt H., Shorter J., Wegrzyn R.D., Andréasson C., Lindquist S. and Bukau B. (2008) Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activities. PloS ONE. 3:e1763

Andréasson C., Fiaux J., Rampelt H., Mayer M.P. and Bukau B. (2008) Hsp110 is a nucleotide-activated exchange factor for Hsp70. J Biol Chem. 283:8877-84.



Cell Biology  Per Ljungdahl, Phone: +46 8 16 41 01

Developmental Biology Christos Samakovlis, Phone: + 46 8 16 15 64

Immunology Marita Troye Blomberg, Phone: + 46 8 16 41 64

Physiology Barbara Cannon, Phone:+ 46 8 16 41 20


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