Open AccessSynthetic protein–protein interaction domains created by shuffling Cys 2 His 2 zinc‐fingers
Author(s) -
Giesecke Astrid V,
Fang Rui,
Joung J Keith
Publication year - 2006
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb4100053
Subject(s) - general hospital , molecular pathology , medical school , medicine , library science , biology , general surgery , genetics , computer science , medical education , gene
Cys 2 His 2 zinc‐fingers (C2H2 ZFs) mediate a wide variety of protein–DNA and protein–protein interactions. DNA‐binding C2H2 ZFs can be shuffled to yield artificial proteins with different DNA‐binding specificities. Here we demonstrate that shuffling of C2H2 ZFs from transcription factor dimerization zinc‐finger (DZF) domains can also yield two‐finger DZFs with novel protein–protein interaction specificities. We show that these synthetic protein–protein interaction domains can be used to mediate activation of a single‐copy reporter gene in bacterial cells and of an endogenous gene in human cells. In addition, the synthetic two‐finger domains we constructed can also be linked together to create more extended, four‐finger interfaces. Our results demonstrate that shuffling of C2H2 ZFs can yield artificial protein‐interaction components that should be useful for applications in synthetic biology.