Research is primarily focused on understanding the mechanisms by which the eukaryotic cell maintains all of its proteins folded and functional. Breakdown of these mechanisms has severe consequences for the cell and results in the accumulation of toxic misfolded and aggregated proteins. Strikingly, protein aggregates are found in the brains of individuals with neurodegenerative disease, e.g. Alzheimer’s and Parkinson’s. Understanding the molecular mechanisms that maintain cellular proteins folded and functional is a fundamental challenge in biological sciences and is crucial in the battle against disease.

Experiments are based on the cytosolic heat-shock protein 70 kDa (Hsp70) class in budding yeast (Saccharomyces cerevisae). Using this experimental model we explore the fundamental mechanisms that maintain the eukaryotic proteome folded and functional. Hsp70 belongs to a group of specialized proteins called molecular chaperones that interact with non-natively folded proteins and promote their folding into native conformations. These interactions form the basis for quality control of cellular proteins; a process in which non-natively proteins are recognized and either are routed to folding promoting pathways or removed from the cell via degradation pathways. 

 

 
A yeast cell in the process of budding off a daugther cell
A yeast cell in the process of budding off a daugther cell with fluorescently labelled protein aggregates (marker protein Hsp104-EGFP). The cell carries a mutation that inactivates the gene encoding Hsp70 nucleotide exchange factor Fes1 (fes1delta).
 

   

Keywords

Hsp70, Protein folding, Protein quality control, Protein degradation, ubiquitin, proteasome

 

Selected publications

Kandasamy G, Andréasson C. (2018) Hsp70-Hsp110 chaperones deliver ubiquitin dependent and independent substrates to the 26S proteasome for proteolysis. J Cell Sci Mar 5. pii: jcs.210948. doi: 10.1242/jcs.210948.

Gowda NKC, Kaimal JM, Kityk R, Daniel C, Liebau J, Öhman M, Mayer MP, Andréasson C. (2018) Nucleotide exchange factors Fes1 and HspBP1 mimic substrate to release misfolded proteins from Hsp70. Nat Struct Mol Biol. Jan;25(1):83-89.

Kaimal JM, Kandasamy G, Gasser F, Andréasson C. (2017) Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae. Mol Cell Biol. May 16;37(11)

Gowda NK, Kaimal JM, Masser AE, Kang W, Friedländer MR, Andréasson C. (2016) Cytosolic splice isoform of Hsp70 nucleotide exchange factor Fes1 is required for the degradation of misfolded proteins in yeast. Mol Biol Cell. Apr 15;27(8):1210-9

Gowda, N.K., Kandasamy, G., Froehlich, M.S., Dohmen, R.J., & Andréasson, C. (2013). Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins. Proc Natl Acad Sci USA. 110(15):5975-80

 

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(Link to ORCID)