RT Journal Article
SR Electronic
T1 Rapid Evolution of Functional Complexity in a Domain Family
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra50
OP ra50
DO 10.1126/scisignal.2000416
VO 2
IS 87
A1 Ernst, Andreas
A1 Sazinsky, Stephen L.
A1 Hui, Shirley
A1 Currell, Bridget
A1 Dharsee, Moyez
A1 Seshagiri, Somasekar
A1 Bader, Gary D.
A1 Sidhu, Sachdev S.
YR 2009
UL http://stke.sciencemag.org/content/2/87/ra50.abstract
AB Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust the binding site must be to produce the rich functional diversity of the natural PDZ domain family. From a combinatorial protein library, we analyzed several hundred structured domain variants and found that one-quarter were functional for carboxyl-terminal ligand recognition and that our variant repertoire was as specific and diverse as the natural family. Our results show that ligand binding is hardwired in the PDZ fold and suggest that this flexibility may facilitate the rapid evolution of complex protein interaction networks.