5KNE

CryoEM Reconstruction of Hsp104 Hexamer

5KNE の概要

• エントリーDOI: 10.2210/pdb5kne/pdb
• EMDBエントリー: 8267
• 分子名称: Heat shock protein 104, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (2 entities in total)
• 機能のキーワード: hsp104, aaa+ protein, chaperone
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 581372.54

構造登録者

Yokom, A.L.,Gates, S.N.,Jackrel, M.E.,Mack, K.L.,Su, M.,Shorter, J.,Southworth, D.R. (登録日: 2016-06-28, 公開日: 2016-07-27, 最終更新日: 2024-03-06)

主引用文献

Yokom, A.L.,Gates, S.N.,Jackrel, M.E.,Mack, K.L.,Su, M.,Shorter, J.,Southworth, D.R.
Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation.
Nat.Struct.Mol.Biol., 23:830-837, 2016

PubMed Abstract: 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.

PubMed: 27478928
DOI: 10.1038/nsmb.3277

実験手法

ELECTRON MICROSCOPY (5.64 Å)