Domain Insertion

These figures complement a recent paper (R. B. Russell, Domain Insertion, Protein Eng. 7, 1407-1410, 1994). This paper was the outcome of my proposal for the EMBL protein design meeting, which I was unfortunately unable to attend. The idea was to design a multidomain protein that comprised the insertion of one domain into another.

These are fairly common occurrences within proteins. The next 5 figures (A-E) give some examples. There are many others out there. Just click on the letters below to see the similarity that is described.

A. Disulphide bond forming protein, DsbA (PDB code 1DSB_A), appears to be the result of inserting a domain from a bacterial zinc metalloproteinase (elastase; 1EZM) into thioredoxin (2TRX):

B. Pyruvate kinase appears to be the result of inserting a domain with a unique topology into N-(5' phosphoribosyl) antranate isomerase.

C. Part of DNA polymerase appears like ribosomal protein L7/L12 with a large domain inserted after the first beta strand.

D. Blue tongue virus coat protein VP7 appear to comprise a novel domain containing an insert very similar to phaseolin.

E.Glutaminyl tRNA synthetase resembles a Rossmann fold, such as that found in glyceraldehyde-3-phosphate dehydrogenase, with an additional domain inserted between the two symmetrical BHBHB repeats.
Baring my soul, here is a hypothetical protein design strategy.