Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation
| Autor: | Xuechao Gao, Matthias P. Mayer, Janine Kirstein, Bernd Bukau, Kristin Arnsburg, Florian Stengel, Antonia Stank, Ruedi Aebersold, Mykhaylo Berynskyy, Annika Scior, Rebecca C. Wade, Anna Szlachcic, D. Lys Guilbride, Nadinath B. Nillegoda, Richard I. Morimoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Protein subunit Static Electricity Plasma protein binding Protein aggregation Protein Aggregation Pathological Nucleotide exchange factor Chaperones Computational models Protein aggregation Protein Aggregates 03 medical and health sciences 0302 clinical medicine Protein structure ddc:570 Animals Humans HSP70 Heat-Shock Proteins HSP110 Heat-Shock Proteins Caenorhabditis elegans 030304 developmental biology 0303 health sciences Multidisciplinary biology biology.organism_classification Protein Structure Tertiary Cell biology Co-chaperone Biochemistry Chaperone (protein) biology.protein 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Nature, 524(7564):247–251 |
| Popis: | Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states1, 2. Healthy metazoan cells effectively eliminate intracellular protein aggregates3, 4, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems5, 6, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro4, 7. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control. published |
| Databáze: | OpenAIRE |
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