Protein domain recruitment

Tsukazaki, T., et al., SARA, a FYVE domain protein that recruits Smad2 to... 

The Stat proteins are found in a latent form in the cytosol and are activated by cytokine receptors and their associated kinases. On binding of the cytokine to the receptor and activation of the Jak kinase, the Stat proteins are recruited, via their SH2 domains, to the receptor-kinase complex and are then phosphorylated by the Jak kinase on a conserved Tyr residue at the C-terminus. 

Tsukazaki, T., Chiang, T.A., Davison, A.F., Attisano, L., and Wrana, J.L. 1998. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell 95 779-791. 

The following sections explore nature s use of domain swapping to evolve new function. These include the formation of multifunctional proteins, tandem duplication, domain recruitment, and cicular permutation (Fig. 1). The evolution of several enzymes in the purine (Fig. 2) and pyrimidine (Fig. 3) de novo biosynthetic pathways, as well as other enzymes, are discussed as illustrative examples. 

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).

The generation of functional versatility in proteins by reorganization of individual protein subunits or domains is summarized under the term domain recruitment . The idea behind domain recruitment has been vividly depicted by Ostermeier and Benkovic s adaptation of the cliche a thousand monkeys typing at a thousand typewriters would eventually reproduce the works of Shakespeare [40]. In reference to domain recruitment, these authors suggest that the writing would obviously work... 

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. 

Tumor necrosis factor receptor-associated protein with death domain, an adapter protein that recruits other proteins to the cytoplasmic TNF (tumor necrosis factor) receptor complex, involved in apoptosis... 

---