I recently followed a protocol from Stephen Sligar's lab for the purification 
of his "nanodisc" protein, which has strong hydrophobic character as it 
associates with phospholipids.  His protocol includes washes with 1% Triton 
X-100 and then with 50 mM cholate (both at pH 8 in the presence of 300 mM 
NaCl).  Worked great, and I saw stuff coming off the column in both washes.  
The reference is:

Bayburt et al. (2002) Nano Letters, vol. 2, pp 853-856.
http://pubs.acs.org/doi/abs/10.1021/nl025623k

Good luck,
Arthur

Arthur Glasfeld
Department of Chemistry
Reed College
3203 SE Woodstock Blvd.
Portland, OR 97202
USA





On Apr 19, 2011, at 12:48 PM, Savvas Savvides wrote:

> Dear colleagues
> 
> We are working on a large bacterial protein (featuring a large number of 
> repeats) that appears to copurify with a lot of other proteins after 
> Ni-affinity chromatography and gel-filtration. We have tried adjusting the 
> ionic strength of these runs and have gone to as high as 5M NaCl but only saw 
> marginal improvements.  It appears that the protein likes to stick to a lot 
> of stuff, and in fact the number of repeats in a given construct appears to 
> correlate with the extent of contaminants in our purification steps. We have 
> admittedly never seen anything like this among the so many different, and 
> often challenging, proteins, we have worked on in our group over the last few 
> years.
> 
> We are now thinking of trying detergents in the buffers (at non-micellar 
> concentrations), in conjunction with playing a bit with the pH to see if such 
> an approach provides a 'stripping' effect. Interestingly, the protein has a 
> calculated pI of 3.5 !
> 
> As the options for handling this protein are indeed quite numerous, we would 
> be grateful for any additional input and possible tips/tricks.
> 
> I will prompty post a summary of the thread.
> 
> Best regards
> Savvas et al.
> 
> 
> ----
> Savvas Savvides
> Unit for Structural Biology @ L-ProBE
> Ghent University
> K.L. Ledeganckstraat 35, 9000 Ghent, Belgium
> Tel/SMS/texting +32  (0)472 928 519
> Skype: savvas.savvides_skype
> http://www.LProBE.ugent.be/xray.html
> 
> 
> 
> 
> 
> 
> 

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