Domain repertoires as a tool to derive protein recognition rules

Several approaches, some of which are described in this issue, have been pr oposed to assemble a complete protein interaction map. These are often base d on high throughput methods that explore the ability of each gene product to bind ally other element of the proteome of the organism. Here we propose that a large number of interactions can be inferred by revealing the rules underlying recognition specificity of a small number (a few hundreds) of f amilies of protein recognition modules, This can be achieved through the co nstruction and characterization of domain repertoires, A domain repertoire is assembled in a combinatorial fashion by allowing each amino acid positio n in the binding site of a given protein recognition domain to vary to incl ude all the residues allowed at that position in the domain family. The rep ertoire is then searched by phage display techniques with any target of int erest and from the primary structure of the binding site of the selected do mains one derives rules that are used to infer the formation of complexes b etween natural proteins in the cell. (C) 2000 Federation of European Bioche mical Societies, Published by Elsevier Science B.V. All rights reserved.