5 ms·
How often do fusion proteins fail to work? I see a lot of "just stick this catalytic domain to dCas9" and I am not really sure why that works.
by kanzure 10y ago
How often do fusion proteins fail to work? I see a lot of "just stick this catalytic domain to dCas9" and I am not really sure why that works.
- jfarlow 10y agoMore times than not protein fusions work just fine for the desired definition of 'work'. If you are trying to tune the very last efficiency out of an enzyme, or push one organism's survival efficiency past another's, then yeah smashing domains together is not the way you arrive at an evolutionarily polished machine. However if you need to test or create new functionality it seems to work just fine. Biology is extraordinarily robust. A common technique is to combine these to approaches - build out a rationally designed functional protein by fusion, then run it through a few rounds of directed evolution to have the organisms themselves iron out the kinks. This strategy has been very successful. Just smashing GFP onto every protein in the yeast proteome resulted in ~80% successfully turning green without noticeably affecting the yeast growth.[1] Check out eCD4-IG - it's four components fused to become an extraordinarily effective anti-HIV drug. It is of a different kind and a different order of effectiveness then the small molecule drugs of the 20th century.[2] [1] http://www.nature.com/nature/journal/v425/n6959/full/nature02046.html http://www.nature.com/nature/journal/v425/n6959/full/nature0... [2] https://serotiny.bio/notes/proteins/ecd4ig/ https://serotiny.bio/notes/proteins/ecd4ig/