A comparison in yeast and human cells reveals a remarkable variability in the properties of RNP granules and highlights a key role for protein disaggregation machines in regulating RNP granule assembly.
Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.
Structural and biochemical studies indicate that AAA+ ATPase employ a general mechanism to translocate a variety of substrates, including extended polypeptides, hairpins, crosslinked chains, and chains conjugated to other molecules.
Cell division imposes a limit on proteostasis capacity by reducing chaperone accumulation, but chaperone-substrate interactions reverse these events to allow clearance of even chronically misfolded protein amyloids.
The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.