Heat-shock protein 104 (Hsp104) and caseinolytic peptidase B (ClpB), members of the AAA+ superfamily, are molecular machines involved in disaggregating insoluble protein aggregates, a process not long ago thought to be impossible. During extreme stress they are essential for cell survival. In addition, Hsp104 regulates prion assembly and disassembly. For most of their protein remodeling activities Hsp104 and ClpB work in collaboration with the Hsp70 or DnaK chaperone systems. Together, the two chaperones catalyze protein disaggregation and reactivation by a mechanism probably involving the extraction of polypeptides from aggregates by forced unfolding and translocation through the Hsp104/ClpB central cavity. The polypeptides are then released back into the cellular milieu for spontaneous or chaperone-mediated refolding.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tibs.2008.09.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single turnover transient state kinetics reveals processive protein unfolding catalyzed by ClpB.
Elife
October 2024
Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States.
ClpB and Hsp104 are AAA+ motor proteins essential for proteome maintenance and thermal tolerance. ClpB and Hsp104 have been proposed to extract a polypeptide from an aggregate and processively translocate the chain through the axial channel of its hexameric ring structure. However, the mechanism of translocation and if this reaction is processive remains disputed.
View Article and Find Full Text PDFAAA+ proteins: one motor, multiple ways to work.
Biochem Soc Trans
April 2022
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
Numerous ATPases associated with diverse cellular activities (AAA+) proteins form hexameric, ring-shaped complexes that function via ATPase-coupled translocation of substrates across the central channel. Cryo-electron microscopy of AAA+ proteins processing substrate has revealed non-symmetric, staircase-like hexameric structures that indicate a sequential clockwise/2-residue step translocation model for these motors. However, for many of the AAA+ proteins that share similar structural features, their translocation properties have not yet been experimentally determined.
View Article and Find Full Text PDFUltrafast pore-loop dynamics in a AAA+ machine point to a Brownian-ratchet mechanism for protein translocation.
Sci Adv
September 2021
Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot 761001, Israel.
AAA+ ring–shaped machines, such as the disaggregation machines ClpB and Hsp104, mediate ATP-driven substrate translocation through their central channel by a set of pore loops. Recent structural studies have suggested a universal hand-over-hand translocation mechanism with slow and rigid subunit motions. However, functional and biophysical studies are in discord with this model.
View Article and Find Full Text PDFHeat Stress Tolerance Gene Affects Conidiation and Pathogenicity of .
Front Microbiol
July 2021
College of Plant Protection, Henan Agricultural University, Zhengzhou, China.
Heat shock protein Hsp104, a homolog of the bacterial chaperone ClpB and plant Hsp100, plays an essential part in the response to heat and various chemical agents in . However, their functions remain largely unknown in plant fungal pathogens. Here, we report the identification and functional characterization of a plausible ortholog of yeast Hsp104 in , which we termed FpHsp104.
View Article and Find Full Text PDFSplit conformation of Chaetomium thermophilum Hsp104 disaggregase.
Structure
July 2021
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
Hsp104 and its bacterial homolog ClpB form hexameric ring structures and mediate protein disaggregation. The disaggregated polypeptide is thought to thread through the central channel of the ring. However, the dynamic behavior of Hsp104 during disaggregation remains unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!