Natural and Designed Proteins Inspired by Extremotolerant Organisms Can Form Condensates and Attenuate Apoptosis in Human Cells.

Autor: Veling MT; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Nguyen DT; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Thadani NN; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States., Oster ME; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Rollins NJ; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Brock KP; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States., Bethel NP; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States., Lim S; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Baker D; Institute for Protein Design, University of Washington, Seattle, Washington 98195, United States.; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States.; Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, United States., Way JC; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States., Marks DS; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, United States., Chang RL; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States.; Department of Systems & Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, United States., Silver PA; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.; Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts 02115, United States.
Jazyk: angličtina
Zdroj: ACS synthetic biology [ACS Synth Biol] 2022 Mar 18; Vol. 11 (3), pp. 1292-1302. Date of Electronic Publication: 2022 Feb 18.
DOI: 10.1021/acssynbio.1c00572
Abstrakt: Many organisms can survive extreme conditions and successfully recover to normal life. This extremotolerant behavior has been attributed in part to repetitive, amphipathic, and intrinsically disordered proteins that are upregulated in the protected state. Here, we assemble a library of approximately 300 naturally occurring and designed extremotolerance-associated proteins to assess their ability to protect human cells from chemically induced apoptosis. We show that several proteins from tardigrades, nematodes, and the Chinese giant salamander are apoptosis-protective. Notably, we identify a region of the human ApoE protein with similarity to extremotolerance-associated proteins that also protects against apoptosis. This region mirrors the phase separation behavior seen with such proteins, like the tardigrade protein CAHS2. Moreover, we identify a synthetic protein, DHR81, that shares this combination of elevated phase separation propensity and apoptosis protection. Finally, we demonstrate that driving protective proteins into the condensate state increases apoptosis protection, and highlights the ability of DHR81 condensates to sequester caspase-7. Taken together, this work draws a link between extremotolerance-associated proteins, condensate formation, and designing human cellular protection.
Databáze: MEDLINE
Externí odkaz: