Biased localization of actin binding proteins by actin filament conformation.

Biased localization of actin binding proteins by actin filament conformation.
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DOI:
10.1038/s41467-020-19768-9
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发表时间:
2020-11-25
影响因子:
16.6
通讯作者:
Fletcher DA
Fletcher DA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Harris AR;Jreij P;Belardi B;Joffe AM;Bausch AR;Fletcher DA

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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. The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology. Here, the authors use a combination of live cell imaging and in vitro single molecule binding measurements to show that tandem calponin homology domains (CH1–CH2) are sensitive to actin filament conformation, biasing their subcellular localization.
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