4WV5

HEAT SHOCK PROTEIN 70 SUBSTRATE BINDING DOMAIN

4WV5 の概要

• エントリーDOI: 10.2210/pdb4wv5/pdb
• 関連するPDBエントリー: 4WV7
• 分子名称: Heat shock 70 kDa protein 1A/1B, GLYCEROL (3 entities in total)
• 機能のキーワード: chaperone
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P08107
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33059.13

構造登録者

Kirby, C.,Stams, T.,Baird, J. (登録日: 2014-11-04, 公開日: 2015-01-14, 最終更新日: 2023-09-27)

主引用文献

Hassan, A.Q.,Kirby, C.A.,Zhou, W.,Schuhmann, T.,Kityk, R.,Kipp, D.R.,Baird, J.,Chen, J.,Chen, Y.,Chung, F.,Hoepfner, D.,Movva, N.R.,Pagliarini, R.,Petersen, F.,Quinn, C.,Quinn, D.,Riedl, R.,Schmitt, E.K.,Schitter, A.,Stams, T.,Studer, C.,Fortin, P.D.,Mayer, M.P.,Sadlish, H.
The novolactone natural product disrupts the allosteric regulation of hsp70.
Chem.Biol., 22:87-97, 2015

PubMed Abstract: The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts.

PubMed: 25544045
DOI: 10.1016/j.chembiol.2014.11.007

実験手法

X-RAY DIFFRACTION (2.04 Å)