Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin
| Autor: | Joel A. Hirsch, Avital Parnas, Iban Ubarretxena-Belandia, Abdussalam Azem, Orna Chomsky-Hecht, Shahar Nisemblat, Malay Patra, Radhika Malik, Fady Jebara, Yacob Gomez-Llorente |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Protein Folding Protein Conformation Science General Physics and Astronomy Cooperativity Ring (chemistry) Crystallography X-Ray Protein Engineering Biochemistry General Biochemistry Genetics and Molecular Biology Article Chaperonin Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Cytosol Chaperonin 10 Humans Nucleotide lcsh:Science chemistry.chemical_classification Multidisciplinary Hydrolysis Cryoelectron Microscopy Cooperative binding Hydrogen Bonding General Chemistry Chaperonin 60 Mitochondria Adenosine Diphosphate 030104 developmental biology chemistry Mitochondrial matrix Biophysics lcsh:Q HSP60 Salt bridge Structural biology 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) 'Nature Communications ', vol: 11, pages: 1916-1-1916-14 (2020) |
| ISSN: | 2041-1723 |
| Popis: | mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins without the negative ATP binding inter-ring cooperativity of GroEL-GroES. Here we report the crystal structure of an ATP (ADP:BeF3-bound) ground-state mimic double-ring mHsp6014-(mHsp107)2 football complex, and the cryo-EM structures of the ADP-bound successor mHsp6014-(mHsp107)2 complex, and a single-ring mHsp607-mHsp107 half-football. The structures explain the nucleotide dependence of mHsp60 ring formation, and reveal an inter-ring nucleotide symmetry consistent with the absence of negative cooperativity. In the ground-state a two-fold symmetric H-bond and a salt bridge stitch the double-rings together, whereas only the H-bond remains as the equatorial gap increases in an ADP football poised to split into half-footballs. Refolding assays demonstrate obligate single- and double-ring mHsp60 variants are active, and complementation analysis in bacteria shows the single-ring variant is as efficient as wild-type mHsp60. Our work provides a structural basis for active single- and double-ring complexes coexisting in the mHsp60-mHsp10 chaperonin reaction cycle. The mHsp60-mHsp10 chaperonin system forms alternating single and double ring complexes to assist protein folding, but the molecular details of this cycle are not fully understood. Here, the authors present cryoEM and crystal structures of key intermediates of the mHsp60-mHsp10 reaction cycle. |
| Databáze: | OpenAIRE |
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