Identification of elements that dictate the specificity of mitochondrial Hsp60 for its co-chaperonin
| Autor: | Peter A. Lund, Amir Pri-Or, Peter Bross, Abdussalam Azem, Shahar Nisemblat, Avital Parnas, Tsaffrir Zor, Galit Levy-Rimler, Celeste Weiss |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Protein Structure Protein Folding Mutant Molecular Sequence Data Biophysics lcsh:Medicine Plasma protein binding macromolecular substances Mitochondrion Biology Bioenergetics Biochemistry Chaperonin Molecular Cell Biology Group I Chaperonins Chaperonin 10 Amino Acid Sequence lcsh:Science Protein Interactions Energy-Producing Organelles Cellular Stress Responses Multidisciplinary Sequence Homology Amino Acid lcsh:R Proteins GroES Chaperonin 60 GroEL Recombinant Proteins Chaperone Proteins Mitochondria Adenosine Diphosphate enzymes and coenzymes (carbohydrates) Mutation biological sciences bacteria lcsh:Q HSP60 Research Article Protein Binding |
| Zdroj: | Parnas, A, Nisemblat, S, Weiss, C, Levy-Rimler, G, Pri-Or, A, Zor, T, Lund, P A, Bross, P & Azem, A 2012, ' Identification of elements that dictate the specificity of mitochondrial Hsp60 for its co-chaperonin ', P L o S One, vol. 7, no. 12, pp. e50318 . https://doi.org/10.1371/journal.pone.0050318 PLoS ONE PLoS ONE, Vol 7, Iss 12, p e50318 (2012) |
| Popis: | Type I chaperonins (cpn60/Hsp60) are essential proteins that mediate the folding of proteins in bacteria, chloroplast and mitochondria. Despite the high sequence homology among chaperonins, the mitochondrial chaperonin system has developed unique properties that distinguish it from the widely-studied bacterial system (GroEL and GroES). The most relevant difference to this study is that mitochondrial chaperonins are able to refold denatured proteins only with the assistance of the mitochondrial co-chaperonin. This is in contrast to the bacterial chaperonin, which is able to function with the help of co-chaperonin from any source. The goal of our work was to determine structural elements that govern the specificity between chaperonin and co-chaperonin pairs using mitochondrial Hsp60 as model system. We used a mutagenesis approach to obtain human mitochondrial Hsp60 mutants that are able to function with the bacterial co-chaperonin, GroES. We isolated two mutants, a single mutant (E321K) and a double mutant (R264K/E358K) that, together with GroES, were able to rescue an E. coli strain, in which the endogenous chaperonin system was silenced. Although the mutations are located in the apical domain of the chaperonin, where the interaction with co-chaperonin takes place, none of the residues are located in positions that are directly responsible for co-chaperonin binding. Moreover, while both mutants were able to function with GroES, they showed distinct functional and structural properties. Our results indicate that the phenotype of the E321K mutant is caused mainly by a profound increase in the binding affinity to all co-chaperonins, while the phenotype of R264K/E358K is caused by a slight increase in affinity toward co-chaperonins that is accompanied by an alteration in the allosteric signal transmitted upon nucleotide binding. The latter changes lead to a great increase in affinity for GroES, with only a minor increase in affinity toward the mammalian mitochondrial co-chaperonin. |
| Databáze: | OpenAIRE |
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