5TTH

Heterodimeric SpyCatcher/SpyTag-fused zebrafish TRAP1 in ATP/ADP-hybrid state

5TTH の概要

• エントリーDOI: 10.2210/pdb5tth/pdb
• 関連するPDBエントリー: 4J0B
• 分子名称: C-terminal SpyCatcher fusion of wildtype zebrafish TNF receptor-associated protein 1, C-terminal Spytag fusion of R417A zebrafish TNF receptor-associated protein 1, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: hsp90, atp, chaperone, trap1, structural genomics, psi-2, protein structure initiative, northeast structural genomics consortium, nesg
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 161302.39

構造登録者

Elnatan, D.,Betegon, M.,Liu, Y.,Agard, D.A.,Northeast Structural Genomics Consortium (NESG) (登録日: 2016-11-03, 公開日: 2017-08-23, 最終更新日: 2024-10-16)

主引用文献

Elnatan, D.,Betegon, M.,Liu, Y.,Ramelot, T.,Kennedy, M.A.,Agard, D.A.
Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1.
Elife, 6:-, 2017

PubMed Abstract: Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate 'client' proteins, facilitating their folding and activating them for biological function. Despite decades of research, the mechanism connecting ATP hydrolysis and chaperone function remains elusive. Particularly puzzling has been the apparent lack of cooperativity in hydrolysis of the ATP in each protomer. A crystal structure of the mitochondrial Hsp90, TRAP1, revealed that the catalytically active state is closed in a highly strained asymmetric conformation. This asymmetry, unobserved in other Hsp90 homologs, is due to buckling of one of the protomers and is most pronounced at the broadly conserved client-binding region. Here, we show that rather than being cooperative or independent, ATP hydrolysis on the two protomers is sequential and deterministic. Moreover, dimer asymmetry sets up differential hydrolysis rates for each protomer, such that the buckled conformation favors ATP hydrolysis. Remarkably, after the first hydrolysis, the dimer undergoes a flip in the asymmetry while remaining in a closed state for the second hydrolysis. From these results, we propose a model where direct coupling of ATP hydrolysis and conformational flipping rearranges client-binding sites, providing a paradigm of how energy from ATP hydrolysis can be used for client remodeling.

PubMed: 28742020
DOI: 10.7554/eLife.25235

実験手法

X-RAY DIFFRACTION (3.2 Å)