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His tag protein binding to resin ... - can i purify off the resin? (Apr/16/2007 )

I am purifying a His tagged protein (46 kD) ... optimized induction conditions & verified with a WB.
When I purify the protein, some of it comes in the flow thru. Nothing in the imidizole fractions. No differential purification with imidizole fractions. Tried all the way from 0 mM to 100 mM imidizole at pH 8.0. Eluted with EDTA ... nothing. I want to avoid denaturing conditions?

I then scooped some of the beads, boiled in in Laemelli, and ran it on a gel. A huge, overwhelming band consisting of pretty much pure target protein!


My Q is: Can I purify the protein from the beads? Maybe using a weak detergent like cholic acid or tween? Will it be functional? Has anone done this?

THanks

Rahul

-rahul chicago-

QUOTE (rahul chicago @ Apr 16 2007, 05:02 PM)
I am purifying a His tagged protein (46 kD) ... optimized induction conditions & verified with a WB.
When I purify the protein, some of it comes in the flow thru. Nothing in the imidizole fractions. No differential purification with imidizole fractions. Tried all the way from 0 mM to 100 mM imidizole at pH 8.0. Eluted with EDTA ... nothing. I want to avoid denaturing conditions?

I then scooped some of the beads, boiled in in Laemelli, and ran it on a gel. A huge, overwhelming band consisting of pretty much pure target protein!


My Q is: Can I purify the protein from the beads? Maybe using a weak detergent like cholic acid or tween? Will it be functional? Has anone done this?

THanks

Rahul


Hi,
try higher concentration of imidazole, we often use 250 mM. In first experiments we determining the correct concentration with a step gradiant from 0-1000mM imidazol (0, 50, 100, 250, 500, 1000)... therefore 100mM could be to low

ms-olli

-ms-olli-

QUOTE (ms-olli @ Apr 16 2007, 12:35 PM)
QUOTE (rahul chicago @ Apr 16 2007, 05:02 PM)
I am purifying a His tagged protein (46 kD) ... optimized induction conditions & verified with a WB.
When I purify the protein, some of it comes in the flow thru. Nothing in the imidizole fractions. No differential purification with imidizole fractions. Tried all the way from 0 mM to 100 mM imidizole at pH 8.0. Eluted with EDTA ... nothing. I want to avoid denaturing conditions?

I then scooped some of the beads, boiled in in Laemelli, and ran it on a gel. A huge, overwhelming band consisting of pretty much pure target protein!


My Q is: Can I purify the protein from the beads? Maybe using a weak detergent like cholic acid or tween? Will it be functional? Has anone done this?

THanks

Rahul


Hi,
try higher concentration of imidazole, we often use 250 mM. In first experiments we determining the correct concentration with a step gradiant from 0-1000mM imidazol (0, 50, 100, 250, 500, 1000)... therefore 100mM could be to low

ms-olli



Also try to combine this approach withpH decreasing till 5.0 -6.0 to change His to uncharged form and weak interaction with resin

-circlepoint-

QUOTE (ms-olli @ Apr 16 2007, 12:35 PM)
QUOTE (rahul chicago @ Apr 16 2007, 05:02 PM)
I am purifying a His tagged protein (46 kD) ... optimized induction conditions & verified with a WB.
When I purify the protein, some of it comes in the flow thru. Nothing in the imidizole fractions. No differential purification with imidizole fractions. Tried all the way from 0 mM to 100 mM imidizole at pH 8.0. Eluted with EDTA ... nothing. I want to avoid denaturing conditions?

I then scooped some of the beads, boiled in in Laemelli, and ran it on a gel. A huge, overwhelming band consisting of pretty much pure target protein!


My Q is: Can I purify the protein from the beads? Maybe using a weak detergent like cholic acid or tween? Will it be functional? Has anone done this?

THanks

Rahul


Hi,
try higher concentration of imidazole, we often use 250 mM. In first experiments we determining the correct concentration with a step gradiant from 0-1000mM imidazol (0, 50, 100, 250, 500, 1000)... therefore 100mM could be to low

ms-olli



I agree,
my His-tagged protein is eluted with
50mM Tris HCl, pH 7,5
150 mM imidazole
300 mM NaCl


...but this is the lowest imidazole concetration

-vankomycine-

we use 250mM imidazole in the elution buffer while purifying through the beads.

-scolix-

im working in protein purification... i cant get my protein in elute.. i used qiagen denaturing methods.. but i failed... what can i do..

-sheha-