5VJH

Closed State CryoEM Reconstruction of Hsp104:ATPyS and FITC casein

Summary for 5VJH

• Entry DOI: 10.2210/pdb5vjh/pdb
• Related: 5VY8 5VY9 5VYA
• EMDB information: 8697 8744 8745 8746
• Descriptor: Heat shock protein 104, FITC casein, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: hsp104, cryoem, aaa+, chaperone
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Cellular location: Cytoplasm: P31539
• Total number of polymer chains: 7
• Total formula weight: 621553.47

Authors

Gates, S.N.,Yokom, A.L.,Lin, J.-B.,Jackrel, M.E.,Rizo, A.N.,Kendsersky, N.M.,Buell, C.E.,Sweeny, E.A.,Chuang, E.,Torrente, M.P.,Mack, K.L.,Su, M.,Shorter, J.,Southworth, D.R. (deposition date: 2017-04-19, release date: 2017-07-05, Last modification date: 2017-08-02)

Primary citation

Gates, S.N.,Yokom, A.L.,Lin, J.,Jackrel, M.E.,Rizo, A.N.,Kendsersky, N.M.,Buell, C.E.,Sweeny, E.A.,Mack, K.L.,Chuang, E.,Torrente, M.P.,Su, M.,Shorter, J.,Southworth, D.R.
Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.
Science, 357:273-279, 2017

PubMed Abstract: Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop-substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.

PubMed: 28619716
DOI: 10.1126/science.aan1052

Experimental method

ELECTRON MICROSCOPY (4 Å)