Circular permutations, protein function

Fig. 1. Schematics of evolutionary mechanisms of domain swapping in nature. Multifunctional proteins arise from the fusion of the genes coding for individual enzymes. Often the individual domains of multifunctional proteins catalyze successive steps in metabolic pathways. In tandem duplication, a gene is duplicated and the 3 end of one copy is fused in-frame to the 5 end of the second copy. In domain recruitment, a functional unit (whole gene or gene fragment) from one gene is either inserted within or fused to an end of a second gene. Circular permuted genes are believed to arise via tandem duplication followed by introduction of new start and stop codons (Ponting el at, 1995).

Evidence for domain recruitment has been identified in a wide variety of proteins [47], mechanistically ranging from simple N- or C-terminal fusion to multiple internal insertions and possibly circular permutations [48]. A recent analysis of proteins in the protein structure database (PDB) has further indicated that structural rearrangements as a result of domain shuffling have significantly contributed to today s functional diversity [49]. A brief overview of the various modes of domain recruitment and their effects on function, is presented on examples of /lex-barrel structures. 

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