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      FIP200-eGFP expression and purification

      Justyna Sawa-Makarska, Eleonora Turco

      Published: 2023-05-24 DOI: 10.17504/protocols.io.dm6gpbkq5lzp/v1
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      Abstract

      This protocol describes how to express and purify human FIP200 tagged C-terminally with eGFP.

      Attachments

      protocols io FIP200.pdf

      Steps

      Expression

      1.

      To generate FIP200-GFP constructs the insect codon optimized FIP200 gene was purchased from GenScript and cloned with respective tags into pGB-02-03 (pGB-GST-3C-FIP200-GFP - Addgene ID: 187830). Generated construct was used for expression in Sf9 insect cells using the Bac-to-Bac system (ThermoFischer Scientific) .

      2.

      Transfect 2.5 μg of bacmid DNA into Sf9 insect cells in 6-well plate using FuGene transfection reagent (Promega).

      3.

      About 7 days after transfection the V0 virus should be ready for harvesting. Use the V0 to produce a V1 virus stock by infecting 30 ml of Sf9 cells (1 million/ml). Collect V1 about 4-5 days later. Monitor viability of the cells and green fluorescence to decide when to collect V1.

      4.

      Infect 1L culture of Sf9 cells at 1-1.5 million/ml cells/volume at 99-100% viability in log phase with 1 ml of Virus 1 (V1).

      5.

      After infection monitor cells for viability and fluorescence. Harvest by centrifugation when the viability drops to 80–95% and clear green fluorescence is present.

      6.

      To harvest spin down the cells at 2000 rpm, for 15 min at RT (Sorvall RC6+ centrifuge, Thermo Scientific). Gently wash the cell pellets with PBS, flash-freeze in liquid nitrogen, and store at −80 °C until purification.

      Purification

      7.

      Thaw a cell pellet corresponding to 1L culture by re-suspending it in 40 ml lysis buffer (50 mM HEPES pH 7.5, 300 mM NaCl, 1 mM MgCl2, 10% glycerol, 0.5% CHAPS, 5 U/ml Benzonase (Sigma), 1 mM DTT, CIP protease inhibitor (Sigma), cOmplete EDTA-free protease inhibitor cocktail (Roche)) and rolling or stirring in the cold room.

      8.

      Additionally disrupt the cells with a Dounce homogenizer followed by 1 min sonication at 50% cycles and 50–60% power.

      9.

      Clear the lysate by centrifugation at 72,000 ×  g for 45 min at 4 °C (Beckman Ti45 rotor)

      10.

      Incubate the cleared supernatant with 5 ml of Glutathione Sepharose 4B beads slurry (Cytiva) overnight at 4°C rolling gently. The GSH slurry should be washed with water and then pre-equillibrated with lysis buffer before incubating with the lysate.

      11.

      Wash the beads seven times with wash buffer (50 mM HEPES pH 7.5, 200 mM NaCl, 1 mM MgCl2, 1 mM DTT).

      12.

      Incubate the beads overnight with preCission 3C protease at 4°C (40 ul of 6 mg/ml home-made protease).

      13.

      Spin down the beads (4000 rpm, 3 min, 4°C) and collect the supernatant containing cleaved FIP200-eGFP.

      14.

      Filter the supernatant through a 0.45 μm syringe filter to remove any residual beads.

      15.

      Concentrate the protein down to 0.5 ml using a 100 kDa cut-off Amicon filter and apply onto a Superose 6 Increase 10/300 column (Cytiva) pre-equillibrated with a SEC buffer containing 25 mM HEPES pH 7.5, 200 mM NaCl, 1 mM DTT. Pool fractions containing pure proteins (see attached pdf), concentrate, snap freeze in liquid nitrogen, and store at −80°C.

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