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DOI | 10.1126/science.aan1052 |
Ratchet-like polypeptide translocation mechanism of the AAA plus disaggregase Hsp104 | |
Gates, Stephanie N.1,2; Yokom, Adam L.1,2; Lin, JiaBei3; Jackrel, Meredith E.3; Rizo, Alexandrea N.2; Kendsersky, Nathan M.3,4; Buell, Courtney E.3; Sweeny, Elizabeth A.3; Mack, Korrie L.3,5; Chuang, Edward3,4; Torrente, Mariana P.3,6,7,8,9; Su, Min1; Shorter, James3,4,5; Southworth, Daniel R.1,2 | |
2017-07-21 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 357期号:6348页码:273-279 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | 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 Saccharomyces cerevisiae 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 aremediated 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000405901600034 |
WOS关键词 | PROTEIN DISAGGREGATION ; 26S PROTEASOME ; INSIGHTS ; CLPB ; CHAPERONE ; HELICASE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/196507 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Michigan, Dept Biol Chem, Inst Life Sci, Ann Arbor, MI 48109 USA; 2.Univ Michigan, Inst Life Sci, Grad Program Chem Biol, Ann Arbor, MI 48109 USA; 3.Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA; 4.Univ Penn, Pharmacol Grad Grp, Perelman Sch Med, Philadelphia, PA 19104 USA; 5.Univ Penn, Biochem & Mol Biophys Grad Grp, Perelman Sch Med, Philadelphia, PA 19104 USA; 6.CUNY Brooklyn Coll, Chem Dept, New York, NY 10016 USA; 7.CUNY, PhD Program Chem, Grad Ctr, New York, NY 10016 USA; 8.CUNY, PhD Program Biochem, Grad Ctr, New York, NY 10016 USA; 9.CUNY, PhD Program Biol, Grad Ctr, New York, NY 10016 USA |
推荐引用方式 GB/T 7714 | Gates, Stephanie N.,Yokom, Adam L.,Lin, JiaBei,et al. Ratchet-like polypeptide translocation mechanism of the AAA plus disaggregase Hsp104[J]. SCIENCE,2017,357(6348):273-279. |
APA | Gates, Stephanie N..,Yokom, Adam L..,Lin, JiaBei.,Jackrel, Meredith E..,Rizo, Alexandrea N..,...&Southworth, Daniel R..(2017).Ratchet-like polypeptide translocation mechanism of the AAA plus disaggregase Hsp104.SCIENCE,357(6348),273-279. |
MLA | Gates, Stephanie N.,et al."Ratchet-like polypeptide translocation mechanism of the AAA plus disaggregase Hsp104".SCIENCE 357.6348(2017):273-279. |
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