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Biased localization of actin binding proteins by actin filament conformation

Journal Article · · Nature Communications
 [1];  [2];  [2];  [2];  [3];  [4]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering and Biophysics Program; OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering and Biophysics Program
  3. Technische Universität München, Garching (Germany). Lehrstuhl für Biophysik (E27)
  4. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering and Biophysics Program; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States)

The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1–CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells. We demonstrate that the binding kinetics of CH1–CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs and other binding proteins. These findings suggest that conformational changes of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF); European Molecular Microbiology Organization (EMBO); Human Frontier Science Program (HFSP); Deutsche Forschungsgemeinschaft (DFG)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1815971
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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