Re: [DIYbio] Re: Do proteins fold differently when folded by different cells?

Is there a quick in silico way to determine whether correct folding of mammalian cells will happen in bacteria? 

On Tue, Oct 3, 2017 at 10:09 AM Mike Horwath <mike...@gmail.com> wrote:

Yeah, "It depends"...one other big reason that mammalian proteins sometimes won't fold in bacteria is disulfide bonds between cysteines, which generally depend on oxidizing enzymes in the ER to form properly. There's kind of a hierarchy for trying different cell types to express human proteins--bacteria if possible, then yeast, then maybe insect cell line, then mammalian cells like chinese hamster ovary.

Mike

On Monday, October 2, 2017 at 5:15:22 AM UTC-4, Ravasz wrote:

I think the correct answer is: "it depends"

For some proteins, you can express them in bacteria or human cells and they will fold in the same manner. But other proteins will fold differently depending on what cell they are expressed in.

This can be due to a number of things. For example some proteins need to be folded into the correct shape by other proteins. Proteins that help other proteins fold correctly are called chaperones. If the chaperone is present in the human cell culture but not in bacteria, then your particular protein will only fold correctly in human cells.

Another reason is post-translational modification, as others have mentioned. After the amino acid chain of a protein is synthesized most proteins will receive phosphorylation, glycosylation, acetylation, methylation, myristoilation and loads of other marks. These modifications will often affect the structure of the protein. Bacteria have a very different system of post-translational modification than human cells, glycosylation being a prime example as stated earlier.

Some proteins require co-factors. These are non-protein molecules that are incorporated into the protein structure. For example, metalloproteases need a certain metal ion to fold correctly. If that particular metal ion is not readily available in the cell you are using, your protein will not fold correctly.

And there are also proteins that should fold in the same manner in both bacteria and human cells but they just don't to annoy you. I hate those proteins.


On Sunday, 1 October 2017 05:52:31 UTC+1, Cory J. Geesaman wrote:

Not necessarily different cells within a single organism, but say you were to splice a really large protein from a Human into a bacteria or the other way around (or any animal or plant or fungus, etc) - when the cell goes to synthesize that protein would it be likely to fold differently?  "Likely" meaning "will it fold differently within that cell type more often than it might misfold otherwise."

If there is a difference in the way proteins are folded between different types of cells, is there any relatively comprehensive list of the differences and members of different groups of protein folding/misfolding mechanics?

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Hans T. Wilms

PhD student, GSU

Charlie Benson Lab

Mobile: (404)-322-5824