Proteins can only perform their complex functions in the cell when they assume a specific three-dimensional structure for each respective task. Because misfolded proteins are often toxic, they are immediately refolded or degraded. Scientists of the Max Planck Institute (MPI) of Biochemistry in Martinsried near Munich have now shown in the yeast model that specific protein aggregates block an important degradation pathway for defective proteins – and thus disrupt the fragile molecular balance of the cell. The results of the study have now been published in the journalCell.
Protein aggregates in cells can cause severe diseases such as Huntington’s disease. The massive movement disorders that appear with this disease are likely caused by aggregates of specific proteins, the polyQ proteins. Scientists of the research department Cellular Biochemistry headed by F.-Ulrich Hartl have now shown how these protein aggregates, commonly known as plaques, seriously disrupt cellular homeostasis.
Cells in the balance
The entire set of all cellular proteins is referred to as the proteome, whose composition is determined by a delicate balance of protein production and degradation. This process is regulated at several levels. Key helpers here are themolecular chaperones which aid the proteins in proper folding or lead them to degradation if the misfolding is irreparable. Among other things, this procedure serves to prevent the formation of protein plaques. Hartl’s team has now succeeded in demonstrating that polyQ aggregates in yeast primarily have an effect on the chaperone Sis1p.
Read more at: Phys.org