YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic


Paper ID: 261

Yeast as a Model to Understand Fundamental Mechanisms of Protein Quality Control 

Hartl F. Ulrich

Max Planck Institute of Biochemistry (Germany)

ABSTRACT

The past two decades have witnessed a paradigm shift in our understanding of cellular protein folding. While the three-dimensional structures of functional proteins are determined by their amino acid sequences, we now know that in the crowded environment of cells newly-synthesized polypeptides depend on molecular chaperone proteins to reach their folded states efficiently and at a biologically relevant time scale. Assistance of protein folding is provided by different types of chaperone which act to prevent misfolding and aggregation, often in an ATP-dependent mechanism. Once folded, many proteins continue to require chaperone surveillance to retain their functional states, especially under conditions of cell stress. Failure of the chaperone machinery to maintain proteostasis, i.e. the conformational integrity and balance of the cellular proteome, facilitates the manifestation of diseases in which proteins misfold and form toxic aggregates. These disorders include Parkinson’s, Huntington’s and Alzheimer’s disease. 

We are using yeast as a model to study the mechanism and consequences of protein aggregation. A focus of ongoing research is on understanding ribosome quality control (RQC). Defects in RQC result in toxic aggregation of nascent polypeptides that stall during translation on ribosomes. These aggregates have features resembling those associated with neurodegenerative disease. 

Balchin D, Hayer-Hartl M, Hartl FU. In vivo aspects of protein folding and quality control.

Science. 2016 Jul 1;353(6294):aac4354. doi: 10.1126/science.aac4354. Review. PMID: 27365453

Choe YJ, Park SH, Hassemer T, Körner R, Vincenz-Donnelly L, Hayer-Hartl M, Hartl FU. Failure of RQC machinery causes protein aggregation and proteotoxic stress. Nature. 2016 Mar 10;531(7593):191-5. doi: 10.1038/nature16973. Epub 2016 Feb 29. PMID: 26934223

Park SH, Kukushkin Y, Gupta R, Chen T, Konagai A, Hipp MS, Hayer-Hartl M, Hartl FU. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone.

Cell. 2013 Jul 3;154(1):134-45. doi: 10.1016/j.cell.2013.06.003. Epub 2013 Jun 20. PMID: 23791384

Keywords:
protein folding, protein aggregation, ribosome quality control, molecular chaperones
Presented as:
  Oral presentation [S5-1] in S5 Cellular strategies of protein quality control

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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