Hi,

Check pI vs pH and try different pH. Can also try room temp purification. 

Try lower salt conc. Is it a DNA-binding protein? Also consider adding a ligand 
or partner if known. Your 10% glycerol should help to improve solubility but 
you can also try 15% glycerol, which should also help in storage/freezing.

Can try adding a little detergent/non-ionic detergent.

Consider different tag (N- vs C-term), construct optimization, engineer 
mutations (happy to elaborate if desired).

Best,
Debanu

> On Dec 24, 2016, at 4:22 PM, Praveen Tripathi <[email protected]> 
> wrote:
> 
> Dear all,
> I am graduate student working on a functional protein which i have cloned in 
> pET-28a vector for recombinant protein production in E.coli expression system.
> The expressed protein is purified on Ni-NTA resins with Imidazole gradient. 
> Surprisingly, i am getting distinct visible white precipitate in pure 
> fractions in eluted fractions itself.
> Please suggest how to make it soluble or how to prevent the precipitation.
> On concentrator the precipitate ration is very much increasing. The protein 
> is pure in soluble as well as precipitate.
> Buffer condition- 50mM Tris(7.5), 500mM NaCl, 10% Glycerol. Elution buffer 
> has varying concentration of imidazole varying from 10mM to 300mM.
>  Any kind of suggestion will be highly appreciated.
> My project requires structure determination.
> 
> Thanks in advance.
> 
> Regards
> Praveen

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