RRC ID 77377
Author Toullec D, Elías-Villalobos A, Faux C, Noly A, Lledo G, Séveno M, Helmlinger D.
Title The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly.
Journal Cell Rep
Abstract Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of kinases that control fundamental processes, including cell growth, DNA damage repair, and gene expression. Although their regulation and activities are well characterized, little is known about how PIKKs fold and assemble into active complexes. Previous work has identified a heat shock protein 90 (Hsp90) cochaperone, the TTT complex, that specifically stabilizes PIKKs. Here, we describe a mechanism by which TTT promotes their de novo maturation in fission yeast. We show that TTT recognizes newly synthesized PIKKs during translation. Although PIKKs form multimeric complexes, we find that they do not engage in cotranslational assembly with their partners. Rather, our findings suggest a model by which TTT protects nascent PIKK polypeptides from misfolding and degradation because PIKKs acquire their native state after translation is terminated. Thus, PIKK maturation and assembly are temporally segregated, suggesting that the biogenesis of large complexes requires both dedicated chaperones and cotranslational interactions between subunits.
Volume 37(3)
Pages 109867
Published 2021-10-19
DOI 10.1016/j.celrep.2021.109867
PII S2211-1247(21)01334-6
PMID 34686329
MeSH Enzyme Stability Gene Expression Regulation, Fungal HSP90 Heat-Shock Proteins / genetics HSP90 Heat-Shock Proteins / metabolism* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Molecular Chaperones / genetics Molecular Chaperones / metabolism* Multiprotein Complexes Protein Binding Protein Kinases / genetics Protein Kinases / metabolism* Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction Telomere-Binding Proteins / genetics Telomere-Binding Proteins / metabolism
IF 8.109
Yeast FY21033