Hi Peter,

You first want to reduce the protein concentration to avoid rapid
precipitation upon adding crystallization solutions.  Try concentrations
of 5 - 10 mg/mL instead of 15 mg/mL.  Next, consider changing the NaCl
concentration.  Salt can act as a co-precipitant, and lowering its
concentration may increase solubility.  Conversely, some proteins
precipitate badly when salt is dialyzed out, so increasing the salt may
also help.  You also may consider using a different pH or different buffer
(HEPES instead of Tris for example).

Glycerol is supposed to make proteins more soluble, but proteins that I
have worked with have turned yellow when concentrated in the presence of
10% glycerol.  Try dialyzing out the glycerol or using a  buffer that does
not contain any glycerol and see if you still see a yellow deposit on the
concentrator or not.  I think that the yellow color is caused by metal
impurities in the glycerol, so using a higher purity glycerol may help
too.

If none of these suggestions help, you may want to consider using a fusion
tag (maltose binding or SUMO) tag for one of your proteins.  These tags
can help increase protein solubility, but unfortunately may also disrupt
protein-protein interactions.

Matt

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