6azy

Crystal structure of Hsp104 R328M/R757M mutant from Calcarisporiella thermophila

spinqualitylabelsall models 6azy, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6azy is a 1 chain structure with sequence from Calcarisporiella thermophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: ADP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A452CSQ7_9FUNG Publication Abstract from PubMed Hsp104 is an AAA+ protein disaggregase with powerful amyloid-remodeling activity. All nonmetazoan eukaryotes express Hsp104 while eubacteria express an Hsp104 ortholog, ClpB. However, most studies have focused on Hsp104 from Saccharomyces cerevisiae and ClpB orthologs from two eubacterial species. Thus, the natural spectrum of Hsp104/ClpB molecular architectures and protein-remodeling activities remains largely unexplored. Here, we report two structures of Hsp104 from the thermophilic fungus Calcarisporiella thermophila (CtHsp104), a 2.70A crystal structure and 4.0A cryo-electron microscopy structure. Both structures reveal left-handed, helical assemblies with all domains clearly resolved. We thus provide the highest resolution and most complete view of Hsp104 hexamers to date. We also establish that CtHsp104 antagonizes several toxic protein-misfolding events in vivo where S. cerevisiae Hsp104 is ineffective, including rescue of TDP-43, polyglutamine, and alpha-synuclein toxicity. We suggest that natural Hsp104 variation is an invaluable, untapped resource for illuminating therapeutic disaggregases for fatal neurodegenerative diseases. Structure of Calcarisporiella thermophila Hsp104 Disaggregase that Antagonizes Diverse Proteotoxic Misfolding Events.,Michalska K, Zhang K, March ZM, Hatzos-Skintges C, Pintilie G, Bigelow L, Castellano LM, Miles LJ, Jackrel ME, Chuang E, Jedrzejczak R, Shorter J, Chiu W, Joachimiak A Structure. 2019 Mar 5;27(3):449-463.e7. doi: 10.1016/j.str.2018.11.001. Epub 2018, Dec 27. PMID:30595457 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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