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Marco Pagliero

How to adjust pH of lysis, binding, and elution buffer for protein...

Ayesha Khan  Follow

Thomas J Esparza In my lab we use sonication to break the cells and get the protein.

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Magnus Alsered  Follow

Dina Fitriana , if you look at the COVID nanobody paper under my profile you can see the method for osmotic shock, which I recommend considering. You would just need to introduce the pelB signal sequence or clone into pET22b or similar vector with pelB.

Regardless, sonication is totally fine to obtain a crude lysate for binding to the Ni-NTA. You can bind the cleared lysate directly by batch binding or running over your column and then performing your normal wash and elution conditions. Let me know if I can be of any additional help.

Best,
Thomas

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Brian McNellis  Follow

Dear W.J. Colonna

Thank you for your answer.
For lysis buffer I am using:
50 mM NaH2PO4, 300 mM NaCl, and 10 mM imidazole, pH 8.0
As for binding and elution buffer I am using the recommendation from the manufacturer’s protocol:
- Binding buffer: 20 mM NaH2PO4, 500 mM NaCl, 20-40 mM imidazole, pH 7.4
- Elution buffer: 20 mM NaH2PO4, 500 mM NaCl, and 500 mM imidazole, pH 7.4

P.S.
Unfortunately, we have never met before, as we are also from different department and Dr. Ratna Hadioetomo retired before I went there for my bachelor’s degree.

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Chemistry point  Follow

Dear Dina Fitriana

you can add in your lysis buffer a good concentrarion of a buffering agent (eg Tris or Phosphate) that is able to maintain the pH stable in a certain range

Generally i use

Tris 20mM, NaCl 300mM and imidazole 10mM pH=8 as binding buffer and solution with same components and pH but different imidazole concentration fo wash and elution

You can prepare all the solutions by mixings the following 3 stock solution

tris 2M pH=8 (prepared using Trisma base and HCl for pH regulation)
imidazole 2M pH=8 (using Hcl for pH regulation)
NaCl 3M (you do not have to regulate

you can find a video about buffer in protein purification at the following link of my blog (ProteoCool)

https://www.blogger.com/video.g?token=AD6v5dzP9DkeYt4nwIFl1pNVQuJw7_vnHlvCcbCTzad5M6URrbtpOEJ9Z5MJ-gTcfR6n06A5fXwQmD5qJtKayesvHrQtqzfE0mhrKxtPpHHuJO0u2FMq9kmvLSz60LTG_RLcHgTUWkY

best regards

Manuele



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Nicola Chambersholder  Follow

4/7/22
Dear Dina,
I have no experience w/ Histrap FF columns and I don't know the recipe or the pH of the binding buffer you are using. For this reason, I don't know why using HCl or NaOH would cause a problem. However, for adjusting buffers, organic acids can be used, as they are weaker than the common mineral acids (HCl, H2SO4, etc.). You can try using acetic acid. This is a weak acid (pK ~1.8 x 10 --5) and can be used to adjust buffer pH, or even to make a buffer (HAc/NAc). Another possibility is boric acid (H3BO3; pK = 6.4 x 10 -10). For weak bases, you can try NaCO3 or NaHCO3.

I hope this information helps you. Good luck w/ your research.

Bill Colonna Iowa State University, Ames, Iowa, USA wcolonna@iastate.edu

P.S.
I see that you attended Bogor University in Indonesia. Did you know Dr. Ratna Hadioetomo? She is a good friend of mine and taught microbiology there for a number of years. She is retired now and may have left the University before you arrived.

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Chux777  Follow

From what you have shown here, there is no reason to adjust your extraction buffer pH. How are you getting your protein out of your cells? We routinely use osmotic shock and directly use the periplasmic fraction for batch binding to Ni-NTA with good yield (5-10mg from a 250mL culture).

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Amy Twining Baum  Follow

In my experience, a French press is safer for proteins than sonication, which can denature.
Why would you change the pH of your buffer? The risk is that addition of acid or base causes local pH-fluctuations that precipitate proteins. If it can't be avoided, at least work with dilute solutions, vigorous stirring and slow addition.
IMHO the better solution is to bind the protein to a matrix and then wash with a buffer that has the new pH. Bound proteins are more stable, and you avoid excessive fluctuation of pH.

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