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Liquid–liquid phase separation of tau protein: The crucial role of electrostatic interactions

Boyko, Solomiia, Qi, Xu, Chen, Tien-Hao, Surewicz, Krystyna, Surewicz, Witold K.·2019·Journal of Biological Chemistry
DOI 10.1074/jbc.ac119.009198PMC PMC6643045
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Figure 1. LLPS of tau441. A, LLPS at different tau441 concentrations as monitored by turbidity (OD at 400 nm) at 37 °C as a function of ionic strength (NaCl concentration) and concentration of the crowding agent, PEG 10,000. Black, 10 mm NaCl; blue, 75 mm NaCl; red, 150 mm NaCl. Error bars, S.D. (n = 5). B, representative fluorescence microscopy images of tau441 under different experimental conditions. The images were obtained at room temperature using a 1:20 ratio of Alexa fluor 488–labeled to unlabeled protein. Scale bar, 3 μm. C, representative FRAP data obtained within 10 min after droplet formation by the addition of 10% PEG. Inset, images of droplets 0 and 40 s after photobleaching (scale bars, 5 μm). A.U., arbitrary units.
Figure 1. LLPS of tau441. A, LLPS at different tau441 concentrations as monitored by turbidity (OD at 400 nm) at 37 °C as a function of ionic strength (NaCl concentration) and concentration of the crowding agent, PEG 10,000. Black, 10 mm NaCl; blue, 75 mm NaCl; red, 150 mm NaCl. Error bars, S.D. (n = 5). B, representative fluorescence microscopy images of tau441 under different experimental conditions. The images were obtained at room temperature using a 1:20 ratio of Alexa fluor 488–labeled to unlabeled protein. Scale bar, 3 μm. C, representative FRAP data obtained within 10 min after droplet formation by the addition of 10% PEG. Inset, images of droplets 0 and 40 s after photobleaching (scale bars, 5 μm). A.U., arbitrary units.CC BY · PubMed Central
Figure 2. The effect of 1,6-hexanediol (1,6-HD) and temperature on LLPS of tau441. A, turbidity in the absence (gray) and presence (red) of 10% (v/w) 1,6-hexanediol. Experiments were performed at 37 °C in the presence of 10% PEG. Error bars, S.D. (n = 5). B, representative fluorescence microscopy images recorded at room temperature in a buffer containing 150 mm NaCl and 10% PEG in the absence (top) and presence of 10% 1,6-hexanediol (bottom). Scale bar, 3 μm. C, turbidity of tau411 (10 μm) in the presence of PEG (10%) as a function of temperature. Samples were prepared by rapidly mixing protein and PEG solutions preheated to 75 °C, and turbidity was monitored in a cooling cycle by decreasing temperature at a rate of 2.5 degrees/min. Error bars, S.D. (n = 4).
Figure 2. The effect of 1,6-hexanediol (1,6-HD) and temperature on LLPS of tau441. A, turbidity in the absence (gray) and presence (red) of 10% (v/w) 1,6-hexanediol. Experiments were performed at 37 °C in the presence of 10% PEG. Error bars, S.D. (n = 5). B, representative fluorescence microscopy images recorded at room temperature in a buffer containing 150 mm NaCl and 10% PEG in the absence (top) and presence of 10% 1,6-hexanediol (bottom). Scale bar, 3 μm. C, turbidity of tau411 (10 μm) in the presence of PEG (10%) as a function of temperature. Samples were prepared by rapidly mixing protein and PEG solutions preheated to 75 °C, and turbidity was monitored in a cooling cycle by decreasing temperature at a rate of 2.5 degrees/min. Error bars, S.D. (n = 4).CC BY · PubMed Central
Figure 3. The effect of truncations and deletions on the propensity of tau441 to undergo LLPS. A, top, net charge per residue (NCPR) plot for tau441 at neutral pH generated using the algorithm available on the CIDER (33) webserver with a five-residue window. Bottom, schematic diagram of tau441 deletion/truncation variants used in this study. B, turbidity of individual tau variants (10 μm in each case) as a function of PEG concentration. Error bars, S.D. (n = 3). C, representative fluorescence microscopy images for different tau variants (10 μm in each case) in the presence of 12% PEG. Scale bars, 3 μm.
Figure 3. The effect of truncations and deletions on the propensity of tau441 to undergo LLPS. A, top, net charge per residue (NCPR) plot for tau441 at neutral pH generated using the algorithm available on the CIDER (33) webserver with a five-residue window. Bottom, schematic diagram of tau441 deletion/truncation variants used in this study. B, turbidity of individual tau variants (10 μm in each case) as a function of PEG concentration. Error bars, S.D. (n = 3). C, representative fluorescence microscopy images for different tau variants (10 μm in each case) in the presence of 12% PEG. Scale bars, 3 μm.CC BY · PubMed Central
Figure 4. The mixture of tauΔ1–117 and tauΔ118–441 undergoes LLPS. A, turbidity of the mixture of tauΔ1–117 and tauΔ118–441 (10 μm each) as a function of PEG concentration. Data for tau441 are shown for comparison. Error bars, S.D. (n = 3). B, representative fluorescence microscopy images showing co-localization of tauΔ1–117 with tauΔ118–441 in liquid droplets. The mixture of two proteins (10 μm each) contained Alexa fluor 488 (tauΔ1–117) and Alexa fluor 594 (tauΔ118–441) variants (5%). The images were obtained at room temperature in the presence of 150 mm NaCl and 12% PEG. Scale bar, 3 μm.
Figure 4. The mixture of tauΔ1–117 and tauΔ118–441 undergoes LLPS. A, turbidity of the mixture of tauΔ1–117 and tauΔ118–441 (10 μm each) as a function of PEG concentration. Data for tau441 are shown for comparison. Error bars, S.D. (n = 3). B, representative fluorescence microscopy images showing co-localization of tauΔ1–117 with tauΔ118–441 in liquid droplets. The mixture of two proteins (10 μm each) contained Alexa fluor 488 (tauΔ1–117) and Alexa fluor 594 (tauΔ118–441) variants (5%). The images were obtained at room temperature in the presence of 150 mm NaCl and 12% PEG. Scale bar, 3 μm.CC BY · PubMed Central

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Research works printed but not linked: 28

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Metadata

Authors
Boyko, S., Qi, X., Chen, T.-H., Surewicz, K., & Surewicz, W. K.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2019-07
Volume
294
Issue
29
Pages
11054-11059
ISSN
0021-9258
DOI
10.1074/jbc.ac119.009198
PMC
PMC6643045
Cited by
271
References
5
Language
en
Licence
Funders
HHS | National Institutes of Health (NIH) (RF1 AG061797)

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