5kne

CryoEM Reconstruction of Hsp104 Hexamer

spinqualitylabelsall models 5kne, resolution 5.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kne is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ANP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HS104_YEAST] Required, in concert with Hsp40 (YDJ1) and Hsp70 (SSA1) and small Hsps (HSP26), for the dissociation, resolubilization and refolding of aggregates of damaged proteins after heat or other environmental stresses. Extracts proteins from aggregates by unfolding and threading them in an ATP-dependent process through the axial channel of the protein hexamer, after which they can be refolded by components of the Hsp70/Hsp40 chaperone system. Substrate binding is ATP-dependent, and release of bound polypeptide is triggered by ATP hydrolysis. Also responsible for the maintenance of prions by dissociating prion fibrils into smaller oligomers, thereby producing transmissible seeds that can infect daughter cells during mitosis and meiosis. Loss of HSP104 can cure yeast cells of the prions [PSI+], [URE3] and [PIN+]. Excess HSP104 can also specifically cure cells of [PSI+]. Publication Abstract from PubMed Hsp104, a conserved AAA+ protein disaggregase, promotes survival during cellular stress. Hsp104 remodels amyloids, thereby supporting prion propagation, and disassembles toxic oligomers associated with neurodegenerative diseases. However, a definitive structural mechanism for its disaggregase activity has remained elusive. We determined the cryo-EM structure of wild-type Saccharomyces cerevisiae Hsp104 in the ATP state, revealing a near-helical hexamer architecture that coordinates the mechanical power of the 12 AAA+ domains for disaggregation. An unprecedented heteromeric AAA+ interaction defines an asymmetric seam in an apparent catalytic arrangement that aligns the domains in a two-turn spiral. N-terminal domains form a broad channel entrance for substrate engagement and Hsp70 interaction. Middle-domain helices bridge adjacent protomers across the nucleotide pocket, thus explaining roles in ATP hydrolysis and protein disaggregation. Remarkably, substrate-binding pore loops line the channel in a spiral arrangement optimized for substrate transfer across the AAA+ domains, thereby establishing a continuous path for polypeptide translocation. Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation.,Yokom AL, Gates SN, Jackrel ME, Mack KL, Su M, Shorter J, Southworth DR Nat Struct Mol Biol. 2016 Aug 1. doi: 10.1038/nsmb.3277. PMID:27478928 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Proteins

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