One of the fundamental enzymatic catalyst assets, which is the most difficult to engineer in synthetic systems, is the coexistence of multifunctional sites and their synergetic cooperation.
The results from the protein microarray analysis indicated that phosphorylated Y992 (pY992) bound to multiple cellular proteins, serving as a multifunctional docking site of EGFR [38].
The TLR4 (TIR domain) carries a multifunctional docking site where MyD88, Mal, TRAM, and TRIF adaptor molecules bind with common specificity [20].
Upon HGF binding, Met undergoes autophosphorylation on several tyrosine residues and constitutes a multifunctional-docking site for adaptor proteins containing the SH2 motif.
Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner.
Most signalling by the Met receptor is mediated by two C-terminal tyrosines, referred to as multifunctional docking sites.
The hypothesis of a multifunctional HN-binding site was later confirmed by site-directed mutagenesis of amino acids in the carbohydrate-binding cavity of NDV-HN which resulted in reduced enzymatic activity, carbohydrate-binding affinity and overall fusogeneity of the associated NDV-F glycoprotein [ 17, 18].
These findings define multifunctional and overlapping sites on the B133 peptide and are useful for designing multifunctional synthetic molecules.
Subsequently, a multifunctional signal transducer docking site is formed by phosphorylation of Y1349 and Y1356 [ 19].
The intracellular aspect contains three further domains: the juxtamembrane region, which is important in downgrading kinase activity following Ser 975 phosphorylation; the catalytic domain that harbours the Y1234 and Y1235 residues; and the multifunctional carboxy-terminal docking site [ 15].
