Non-ergodicity of a globular protein extending beyond its functional timescale
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- School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China
- Interdisciplinary Research Center on Biology and Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China, University of the Chinese Academy of Sciences, Beijing 100049, China
- Mathematical BioPhysics Group, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany
- Department of Physics, North Carolina State University, Raleigh, NC 27695, USA
- Interdisciplinary Research Center on Biology and Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China
- UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA, Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996, USA
- School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China, Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China
Internal motions of folded proteins have been assumed to be ergodic, i.e., that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynamics (MD) simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), we demonstrate that the functional inter-domain motion is observationally non-ergodic over the time spans 10–12 to 10–7 s and 10–1 to 102 s. The difference between observational non-ergodicity and simple non-convergence is discussed. In comparison, a single-strand DNA of similar size behaves ergodically with an energy landscape resembling a one-dimensional linear chain. The observed non-ergodicity results from the hierarchical connectivity of the high-dimensional energy landscape of the protein molecule. As the characteristic time for the protein to conduct its dephosphorylation function is ~10 s, our findings suggest that, due to the non-ergodicity, individual, seemingly identical protein molecules can be dynamically and functionally different.
- Research Organization:
- Univ. of Tennessee, Knoxville, TN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Natural Science Foundation of China (NSFC); Shanghai Municipal Education Commission; Shanghai Jiao Tong University; German Research Foundation (DFG)
- Grant/Contract Number:
- 11974239; 31630002; 2016QN13
- OSTI ID:
- 1880399
- Alternate ID(s):
- OSTI ID: 1904054
- Journal Information:
- Chemical Science, Journal Name: Chemical Science Vol. 13 Journal Issue: 33; ISSN 2041-6520
- Publisher:
- Royal Society of Chemistry (RSC)Copyright Statement
- Country of Publication:
- United Kingdom
- Language:
- English
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