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Nat Struct Biol. 2002 Aug;9(8):621-7.

Computer-aided design of a PDZ domain to recognize new target sequences.

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Cell Biology and Biophysics Program, EMBL, 69117 Heidelberg, Germany.


PDZ domains are small globular domains that recognize the last 4-7 amino acids at the C-terminus of target proteins. The specificity of the PDZ-ligand recognition is due to side chain-side chain interactions, as well as the positioning of an alpha-helix involved in ligand binding. We have used computer-aided protein design to produce mutant versions of a Class I PDZ domain that bind to novel Class I and Class II target sequences both in vitro and in vivo, thus providing an alternative to primary antibodies in western blotting, affinity chromatography and pull-down experiments. Our results suggest that by combining different backbone templates with computer-aided protein design, PDZ domains could be engineered to specifically recognize a large number of proteins.

[Indexed for MEDLINE]

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