Dear Pascal,
be aware that fos-choline detergents are extremely efficient solubilizers of membrane proteins. We found that even partially aggregated membrane proteins could be solubilized with fos-choline 12, while this fraction did sediment using for example dodecylmaltoside (see e.g. fig5 and sfig2 of PNAS,2008;105(15):5722-7; PMID: 18391190). Thus, it might be that your protein is not expressed in a well-folded state, but that it is (partially) aggregated thereby obscuring the His-tag and preventing binding to the column. To determine whether this is the case you could put a fraction of your high-spin supernatant after solubilization on SEC column and detect the protein by immunoblotting the fractions. If most of the protein elutes in the void this is a strong indication that your protein is not expressed in a good state.
Good luck,
Eric
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