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-Structure paper
タイトル | Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. |
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ジャーナル・号・ページ | Science, Vol. 357, Issue 6348, Page 273-279, Year 2017 |
掲載日 | 2017年7月21日 |
著者 | Stephanie N Gates / Adam L Yokom / JiaBei Lin / Meredith E Jackrel / Alexandrea N Rizo / Nathan M Kendsersky / Courtney E Buell / Elizabeth A Sweeny / Korrie L Mack / Edward Chuang / Mariana P Torrente / Min Su / James Shorter / Daniel R Southworth / |
PubMed 要旨 | Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and ...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. |
リンク | Science / PubMed:28619716 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.0 - 6.7 Å |
構造データ | EMDB-8697, PDB-5vjh: |
化合物 | ChemComp-AGS: ChemComp-ADP: |
由来 |
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キーワード | CHAPERONE / Hsp104 / cryoem / AAA+ |