Spiraling in control: structures and mechanisms of the Hsp104 disaggregase

J Shorter, DR Southworth - Cold Spring Harbor …, 2019 - cshperspectives.cshlp.org
Hsp104 is a hexameric AAA+ ATPase and protein disaggregase found in yeast, which
couples ATP hydrolysis to the dissolution of diverse polypeptides trapped in toxic …

Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins

RUH Mattoo, P Goloubinoff - Cellular and Molecular Life Sciences, 2014 - Springer
By virtue of their general ability to bind (hold) translocating or unfolding polypeptides
otherwise doomed to aggregate, molecular chaperones are commonly dubbed “holdases” …

Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations

RR Cupo, J Shorter - Elife, 2020 - elifesciences.org
Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation
and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase …

Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation

M Carroni, E Kummer, Y Oguchi, P Wendler, DK Clare… - Elife, 2014 - elifesciences.org
The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with
the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled …

AAA+ proteins: one motor, multiple ways to work

JB Lin, J Shorter, AL Lucius - Biochemical Society Transactions, 2022 - portlandpress.com
Numerous ATPases associated with diverse cellular activities (AAA+) proteins form
hexameric, ring-shaped complexes that function via ATPase-coupled translocation of …

Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation

AL Yokom, SN Gates, ME Jackrel, KL Mack… - Nature structural & …, 2016 - nature.com
Hsp104, a conserved AAA+ protein disaggregase, promotes survival during cellular stress.
Hsp104 remodels amyloids, thereby supporting prion propagation, and disassembles toxic …

Mechanistic and structural insights into the prion-disaggregase activity of Hsp104

EA Sweeny, J Shorter - Journal of molecular biology, 2016 - Elsevier
Hsp104 is a dynamic ring translocase and hexameric AAA+ protein found in yeast, which
couples ATP hydrolysis to disassembly and reactivation of proteins trapped in soluble …

The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation

EA Sweeny, ME Jackrel, MS Go, MA Sochor, BM Razzo… - Molecular cell, 2015 - cell.com
The structural basis by which Hsp104 dissolves disordered aggregates and prions is
unknown. A single subunit within the Hsp104 hexamer can solubilize disordered …

Mining disaggregase sequence space to safely counter TDP-43, FUS, and α-synuclein proteotoxicity

A Tariq, JB Lin, ME Jackrel, CD Hesketh, PJ Carman… - Cell reports, 2019 - cell.com
Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in
its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α …

Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB deficiency

SB Wortmann, S Ziętkiewicz, S Guerrero-Castillo… - Genetics in …, 2021 - nature.com
Purpose To investigate monoallelic CLPB variants. Pathogenic variants in many genes
cause congenital neutropenia. While most patients exhibit isolated hematological …