Visualizing chaperone-assisted protein folding

Horowitz, Scott; Salmon, Loïc; Koldewey, Philipp; Ahlstrom, Logan S.; Martin, Raoul; Quan, Shu; Afonine, Pavel V.; van den Bedem, Henry; Wang, Lili; Xu, Qingping; Trievel, Raymond C.; Brooks, Charles L.; Bardwell, James C. A.

doi:10.1038/nsmb.3237

Visualizing chaperone-assisted protein folding

Journal Article · Mon May 30 00:00:00 EDT 2016 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.3237· OSTI ID:1379420

Horowitz, Scott ^[1]; Salmon, Loïc ^[1]; Koldewey, Philipp ^[1]; Ahlstrom, Logan S. ^[2]; Martin, Raoul ^[1]; Quan, Shu ^[3]; Afonine, Pavel V. ^[4]; ^[5]; Wang, Lili ^[1]; Xu, Qingping ^[6]; Trievel, Raymond C. ^[7]; Brooks, Charles L. ^[2]; Bardwell, James C. A. ^[1]

Univ. of Michigan, Ann Arbor, MI (United States). Department of Molecular, Cellular, and Developmental Biology; Howard Hughes Medical Inst., Ann Arbor, MI (United States)
Univ. of Michigan, Ann Arbor, MI (United States). Department of Chemistry and Biophysics Program
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing, Shanghai (China)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
SLAC National Accelerator Lab., Menlo Park, CA (United States). Division of Biosciences
SLAC National Accelerator Lab., Menlo Park, CA (United States). Joint Center for Structural Genomics, Stanford Synchrotron Radiation Lightsource
Univ. of Michigan, Ann Arbor, MI (United States). Department of Biological Chemistry

We present that challenges in determining the structures of heterogeneous and dynamic protein complexes have greatly hampered past efforts to obtain a mechanistic understanding of many important biological processes. One such process is chaperone-assisted protein folding. Obtaining structural ensembles of chaperone–substrate complexes would ultimately reveal how chaperones help proteins fold into their native state. To address this problem, we devised a new structural biology approach based on X-ray crystallography, termed residual electron and anomalous density (READ). READ enabled us to visualize even sparsely populated conformations of the substrate protein immunity protein 7 (Im7) in complex with the Escherichia coli chaperone Spy, and to capture a series of snapshots depicting the various folding states of Im7 bound to Spy. The ensemble shows that Spy-associated Im7 samples conformations ranging from unfolded to partially folded to native-like states and reveals how a substrate can explore its folding landscape while being bound to a chaperone.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 1379420

Alternate ID(s):: OSTI ID: 1419059

Journal Information:: Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 7 Vol. 23; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Selecting Conformational Ensembles Using Residual Electron and Anomalous Density (READ) Salmon, Loïc; Ahlstrom, Logan S.; Bardwell, James C. A. Protein Complex Assembly https://doi.org/10.1007/978-1-4939-7759-8_31	book	January 2018
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Protein folding while chaperone bound is dependent on weak interactions Wu, Kevin; Stull, Frederick; Lee, Changhan Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12774-6	journal	October 2019
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Reply to ‘Misreading chaperone–substrate complexes from random noise’ Horowitz, Scott; Salmon, Loïc; Koldewey, Philipp Nature Structural & Molecular Biology, Vol. 25, Issue 11 https://doi.org/10.1038/s41594-018-0145-2	journal	October 2018
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A molecular mechanism of chaperone–client recognition He, Lichun; Sharpe, Timothy; Mazur, Adam American Association for the Advancement of Science https://doi.org/10.5451/unibas-ep53663	text	January 2016

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