Naslov
Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes

Autori
Finka, Andrija ; Mattoo, Rayees U.H. ; Goloubinoff, Pierre

Kolaboracija
University Of Lausanne, Switzerland

Izvornik
Annual Review of Biochemistry (0066-4154) 85 (2016), 1; 715-742

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
heat-shock proteinsHsp60Hsp70Hsp110Hsp104small heat-shock proteinssHspsprotein homeostasisunfoldases

Sažetak
Molecular chaperones control the cellular folding, assembly, unfolding, disassembly, translocation, activation, inactivation, disaggregation, and degradation of proteins. In 1989, groundbreaking experiments demonstrated that a purified chaperone can bind and prevent the aggregation of artificially unfolded polypeptides and use ATP to dissociate and convert them into native proteins. A decade later, other chaperones were shown to use ATP hydrolysis to unfold and solubilize stable protein aggregates, leading to their native re-folding. Presently, the main conserved chaperone families Hsp70, Hsp104, Hsp90, Hsp60, and small heat-shock proteins (sHsps) apparently act as unfolding nanomachines capable of converting functional alternatively folded or toxic misfolded polypeptides into harmless protease-degradable or biologically active native proteins. Being unfoldases, the chaperones can proofread three-dimensional protein structures and thus control protein quality in the cell. Understanding the mechanisms of the cellular unfoldases is central to the design of new therapies against aging, degenerative protein conformational diseases, and specific cancers.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA