8P66
Structural basis of aggregate binding/recognition by the AAA+ disaggregase ClpG
Summary for 8P66
| Entry DOI | 10.2210/pdb8p66/pdb |
| NMR Information | BMRB: 34818 |
| Descriptor | Clp protease ClpC,Heat shock survival AAA family ATPase ClpK, ZINC ION (2 entities in total) |
| Functional Keywords | atpase associated with diverse cellular activities (aaa), protein aggregation, molecular chaperone, stress, 70 kilodalton heat shock protein (hsp70), chaperone |
| Biological source | Pseudomonas aeruginosa More |
| Total number of polymer chains | 1 |
| Total formula weight | 6457.77 |
| Authors | Simon, B.,Hennig, J.,Mogk, A. (deposition date: 2023-05-25, release date: 2023-11-01, Last modification date: 2023-11-22) |
| Primary citation | Katikaridis, P.,Simon, B.,Jenne, T.,Moon, S.,Lee, C.,Hennig, J.,Mogk, A. Structural basis of aggregate binding by the AAA+ disaggregase ClpG. J.Biol.Chem., 299:105336-105336, 2023 Cited by PubMed Abstract: Severe heat stress causes massive loss of essential proteins by aggregation, necessitating a cellular activity that rescues aggregated proteins. This activity is executed by ATP-dependent, ring-forming, hexameric AAA+ disaggregases. Little is known about the recognition principles of stress-induced protein aggregates. How can disaggregases specifically target aggregated proteins, while avoiding binding to soluble non-native proteins? Here, we determined by NMR spectroscopy the core structure of the aggregate-targeting N1 domain of the bacterial AAA+ disaggregase ClpG, which confers extreme heat resistance to bacteria. N1 harbors a Zn-coordination site that is crucial for structural integrity and disaggregase functionality. We found that conserved hydrophobic N1 residues located on a β-strand are crucial for aggregate targeting and disaggregation activity. Analysis of mixed hexamers consisting of full-length and N1-truncated subunits revealed that a minimal number of four N1 domains must be present in a AAA+ ring for high-disaggregation activity. We suggest that multiple N1 domains increase substrate affinity through avidity effects. These findings define the recognition principle of a protein aggregate by a disaggregase, involving simultaneous contacts with multiple hydrophobic substrate patches located in close vicinity on an aggregate surface. This binding mode ensures selectivity for aggregated proteins while sparing soluble, non-native protein structures from disaggregase activity. PubMed: 37827289DOI: 10.1016/j.jbc.2023.105336 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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