4IPE

Crystal structure of mitochondrial Hsp90 (TRAP1) with AMPPNP

4IPE の概要

• エントリーDOI: 10.2210/pdb4ipe/pdb
• 分子名称: TNF receptor-associated protein 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: chaperone, atpase, atp binding, mitochondria
• 由来する生物種: Danio rerio (leopard danio,zebra danio,zebra fish)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 165757.55

構造登録者

Partridge, J.R.,Lavery, L.A.,Agard, D.A. (登録日: 2013-01-09, 公開日: 2014-01-22, 最終更新日: 2014-08-27)

主引用文献

Lavery, L.A.,Partridge, J.R.,Ramelot, T.A.,Elnatan, D.,Kennedy, M.A.,Agard, D.A.
Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism.
Mol.Cell, 53:330-343, 2014

PubMed Abstract: While structural symmetry is a prevailing feature of homo-oligomeric proteins, asymmetry provides unique mechanistic opportunities. We present the crystal structure of full-length TRAP1, the mitochondrial Hsp90 molecular chaperone, in a catalytically active closed state. The TRAP1 homodimer adopts a distinct, asymmetric conformation, where one protomer is reconfigured via a helix swap at the middle:C-terminal domain (MD:CTD) interface. This interface plays a critical role in client binding. Solution methods validate the asymmetry and show extension to Hsp90 homologs. Point mutations that disrupt unique contacts at each MD:CTD interface reduce catalytic activity and substrate binding and demonstrate that each protomer needs access to both conformations. Crystallographic data on a dimeric NTD:MD fragment suggests that asymmetry arises from strain induced by simultaneous NTD and CTD dimerization. The observed asymmetry provides the potential for an additional step in the ATPase cycle, allowing sequential ATP hydrolysis steps to drive both client remodeling and client release.

PubMed: 24462206
DOI: 10.1016/j.molcel.2013.12.023

実験手法

X-RAY DIFFRACTION (2.289 Å)