5VY9

S. cerevisiae Hsp104:casein complex, Middle Domain Conformation

5VY9 の概要

• エントリーDOI: 10.2210/pdb5vy9/pdb
• 関連するPDBエントリー: 5VJH 5vy8 5vya
• EMDBエントリー: 8697 8744 8745 8746
• 分子名称: Heat shock protein 104, Alpha-S1-casein, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: hsp104, cryoem, aaa+, chaperone
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 621723.68

構造登録者

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. (登録日: 2017-05-24, 公開日: 2017-07-19, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (6.7 Å)