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Cited by 160

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Structural Asymmetry in the Closed State of Mitochondrial Hsp90 (TRAP1) Supports a Two-Step ATP Hydrolysis Mechanism

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Lavery, Laura A., Partridge, James R., Ramelot, Theresa A., Elnatan, Daniel, Kennedy, Michael A., Agard, David A.·2014·Molecular Cell
DOI 10.1016/j.molcel.2013.12.023
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Abstract

Summary 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. Importantly, 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, 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.

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Metadata

Authors
Lavery, L. A., Partridge, J. R., Ramelot, T. A., Elnatan, D., Kennedy, M. A., & Agard, D. A.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2014-01
Volume
53
Issue
2
Pages
330-343
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2013.12.023
OpenAlex
W2021440731
Cited by
160
References
11
FWCI
6.21
Type
journal article
Language
en
Open access
bronze
Licence

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CoChat. (2026). Citation check: Structural Asymmetry in the Closed State of Mitochondrial Hsp90 (TRAP1) Supports a Two-Step ATP Hydrolysis Mechanism. https://app.cochat.ai/papers/10.1016/j.molcel.2013.12.023
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Lavery, L. A., Partridge, J. R., Ramelot, T. A., Elnatan, D., Kennedy, M. A., & Agard, D. A. (2014). Structural Asymmetry in the Closed State of Mitochondrial Hsp90 (TRAP1) Supports a Two-Step ATP Hydrolysis Mechanism. Molecular Cell. https://doi.org/10.1016/j.molcel.2013.12.023

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