Visualizing chaperone-assisted protein folding
- 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.
- 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
- Journal Information:
- Nature Structural & Molecular Biology, Vol. 23, Issue 7; ISSN 1545-9993
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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