Largest deletion leaving a functional protein

Dennis J. Templeton djt2 at po.CWRU.Edu
Sat Oct 12 14:10:10 EST 1991


In a previous article, micprf at lure.latrobe.edu.au () says:

>Greetings,
>	A colleague of mine was telling me recently about a cloned gene
>that encoded a truncated protein (I can't remember what it was) which
>remained functional in the phenotypic test despite having 45% of its
>sequence gone (C terminal end I think). This has me wondering how common
>it is for proteins missing large parts of the original sequence to remain
>functionally intact, and what the record is for the largest deletion
>that still left a functional gene product. I thought this might be a fun
>topic for discussion on the net.		Cheers, Paul Fisher.
>

Paul...

This is going to result in a semantic discussion...  What do you mean by 
"functional"?

Since most(?) proteins are compose of distinct domains, if one is interested
in the "function" of a single domain one could theoretically delete
all other domains of the protein and still retain function.  A good example
is that of the multifunctional viral oncoprotein E1A, which (amoung other
things) binds to and presumably inactivates the retinoblastoma tumor
suppressor protein.  The domain of E1A responsible for this activity is
quite small, and a synthetic 10 or 12 aa peptide is able to perform this
"function" as measured in vitro.

Clearly an enzymatic activity will require  both substrate binding domains
and catalytic domains, but also will probably have regulatory domains that
are likely to be poorly understood.  If one deleted the regulatory domains
one might conclude that the "function" of the enzyme is retained, but
clearly something is lost.

I remain of the mind that Nature has trimmed most proteins to the structure
best suited to promoting life, and that that will become more evident as we
understand protein structure better.

Dennis Templeton



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