Dear Shijun,
Just a reminder that the pI calculated from the sequence is not necessarily the 
real pI, and sometimes can very quite a bit due to folding and oligomerization 
of the protein. The first protein I ever expressed had a calculated pI of 9.2 
and a real pI of 7.8 (if I remember correctly), so the difference can be quite 
large. You can determine the real pI by iso-electric focussing. 
Best wishes,
Mark

Mark J van Raaij
Dpto de Estructura de Macromoleculas
Centro Nacional de Biotecnologia - CSIC
calle Darwin 3
E-28049 Madrid, Spain
tel. (+34) 91 585 4616
Section Editor Acta Crystallographica F
https://journals.iucr.org/f/


> On 20 Jul 2020, at 08:38, 张士军 <[email protected]> wrote:
> 
> Dear:
> 
> The protein was purified in 4 degree, and the expression level is low, so the 
> aggregation is not by high concentration; the buffer pH is 7.5 which is not 
> colse to the PI 8.6. It should be a dimer when function, but it was 
> aggregated when negative staining. Maybe I could try to add arginine when 
> purification, or do mutantions. anyone has website for prediction the 
> mutation sites of protein?
> 
> Thanks!
> 
> Best,
> 
> shijun
> 
> 
> 
> -----原始邮件-----
> 发件人:"Nikolay Dobrev" <[email protected]>
> 发送时间:2020-07-19 20:29:49 (星期日)
> 收件人: [email protected]
> 抄送: 
> 主题: Re: [ccp4bb] protein oligomer
> 
> It really depends from the nature of the protein and if is 
> oligomerizing/agregating/forming polymers if any of this is reversible.
> On the other side if you are working with one of the fibril forming protein 
> it will require optimizaiton on its on as they will form naturally polymers.
> 
> Do you observed different specises when you analyze your protein by SEC or if 
> you are able to perfom DLS?
> Additional information regarding your protein will be really helpful for more 
> detalied suggestions how to overcome your protein.
> 
> Best,
> Nikolay
> 
> Nikolay Dobrev 
> Scientific Officer, Protein Expression and Purification Core Facility
> EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
> T +49 6221 387 8633 | M +49 173 684 0532
> twitter.com/EMBLorg | facebook.com/embl.org | youtube.com/user/emblmedia
> Visit www.embl.org/events <http://www.embl.org/events> for a complete list of 
> all EMBL events.
> 
> On 19/07/2020 14:15, S. Mohanty wrote:
>> Keep the protein concentration low during purification steps along with 
>> using other anti-aggregation agent/s. Make sure that the pH at which you are 
>> purifying is not close to the pI of the protein. Until completely purified, 
>> all purification steps should be performed in a cold room if it is a soluble 
>> protein.
>> 
>> Smita 
>> 
>> 
>> On Sunday, July 19, 2020, 04:28:45 AM CDT, Sorin Draga <[email protected]> 
>> <mailto:[email protected]> wrote:
>> 
>> 
>> I am not sure what you mean by polymer formation. Presuming that you have 
>> optimized your protein concentration, pH and salt concentration, you could 
>> try arginine as an anti-aggregation agent in your purification (I presume 
>> you do FPLC). Have a look at chaotropic agents used in protein purification, 
>> The answer is generally dependent on the protein/proteins you are trying to 
>> purify and is not necessarily straightforward.
>> 
>> Kinds regards
>> 
>> On Sun, Jul 19, 2020 at 12:08 PM 张士军 <[email protected] 
>> <mailto:[email protected]>> wrote:
>> Dear all:
>> 
>> Any ideas to decrease protein polymer formation? my protein was easy to form 
>> oligomers and precipitation when do purification,I have tried add glycerol 
>> and DTT,both didn't work. Does anyone has experience to avoid it happening. 
>> Thanks!
>> 
>> Best Regards
>> 
>> 
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> Nikolay Dobrev 
> Scientific Officer, Protein Expression and Purification Core Facility
> EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
> T +49 6221 387 8633 | M +49 173 684 0532
> twitter.com/EMBLorg | facebook.com/embl.org | youtube.com/user/emblmedia
> Visit www.embl.org/events <http://www.embl.org/events> for a complete list of 
> all EMBL events.
> 
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