Nejvíce citovaný článek - PubMed ID 30917858
Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage
Translocase of outer mitochondrial membrane 34 (TOMM34) orchestrates heat shock protein 70 (HSP70)/HSP90-mediated transport of mitochondrial precursor proteins. Here, using in vitro phosphorylation and refolding assays, analytical size-exclusion chromatography, and hydrogen/deuterium exchange MS, we found that TOMM34 associates with 14-3-3 proteins after its phosphorylation by protein kinase A (PKA). PKA preferentially targeted two serine residues in TOMM34: Ser93 and Ser160, located in the tetratricopeptide repeat 1 (TPR1) domain and the interdomain linker, respectively. Both of these residues were necessary for efficient 14-3-3 protein binding. We determined that phosphorylation-induced structural changes in TOMM34 are further augmented by binding to 14-3-3, leading to destabilization of TOMM34's secondary structure. We also observed that this interaction with 14-3-3 occludes the TOMM34 interaction interface with ATP-bound HSP70 dimers, which leaves them intact and thereby eliminates an inhibitory effect of TOMM34 on HSP70-mediated refolding in vitro In contrast, we noted that TOMM34 in complex with 14-3-3 could bind HSP90. Both TOMM34 and 14-3-3 participated in cytosolic precursor protein transport mediated by the coordinated activities of HSP70 and HSP90. Our results provide important insights into how PKA-mediated phosphorylation and 14-3-3 binding regulate the availability of TOMM34 for its interaction with HSP70.
- Klíčová slova
- 14-3-3 protein, 70-kDa heat shock protein (Hsp70), HSP70, Hsp70, Tomm34, dimerization, hydrogen-deuterium exchange, molecular chaperone, phosphorylation, protein folding, protein import, protein kinase A (PKA), protein-nucleic acid interaction, protein–protein interaction, translocase of outer mitochondrial membrane 34 (TOMM34),
- MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- fosforylace fyziologie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- mitochondriální importní komplex MeSH
- mitochondriální membrány metabolismus MeSH
- mitochondriální proteiny metabolismus MeSH
- molekulární chaperony metabolismus MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- proteiny 14-3-3 metabolismus MeSH
- proteiny tepelného šoku HSP70 metabolismus MeSH
- proteiny tepelného šoku HSP72 metabolismus MeSH
- proteiny tepelného šoku HSP90 metabolismus MeSH
- signální transdukce MeSH
- transkripční faktory genetika metabolismus MeSH
- transportní proteiny mitochondriální membrány genetika metabolismus MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BCL2-associated athanogene 1 protein MeSH Prohlížeč
- DNA vazebné proteiny MeSH
- mitochondriální importní komplex MeSH
- mitochondriální proteiny MeSH
- molekulární chaperony MeSH
- proteinkinasy závislé na cyklickém AMP MeSH
- proteiny 14-3-3 MeSH
- proteiny tepelného šoku HSP70 MeSH
- proteiny tepelného šoku HSP72 MeSH
- proteiny tepelného šoku HSP90 MeSH
- TOMM34 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
- transportní proteiny mitochondriální membrány MeSH