Journal
ACS CHEMICAL BIOLOGY
Volume 5, Issue 6, Pages 545-552Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb9002464
Keywords
-
Categories
Funding
- Yale-HHMI Future Scientist Summer Fellowship
- Michael Manzella Foundation
- Sheffield Society
- Science, Technology, and Research Scholars (STARS) II Fellowship
- National Institutes of Health [R01 GM083050]
- HFSP
Ask authors/readers for more resources
A major challenge of protein design is to create useful new proteins that interact specifically with biological targets in living cells. Such binding modules have many potential applications, including the targeted perturbation of protein networks. As a general approach to create such modules, we designed a library with approximately 10(9) different binding specificities based on a small 3-tetratricopeptide repeat (TPR) motif framework. We employed a novel strategy, based on split GFP reassembly, to screen the library for modules with the desired binding specificity. Using this approach, we identified modules that bind tightly and specifically to Dss1, a small human protein that interacts with the tumor suppressor protein BRCA2. We showed that these modules also bind the yeast homologue of Dss1, Semi. Furthermore, we demonstrated that these modules inhibit Semi activity in yeast. This strategy will be generally applicable to make novel genetically encoded tools for systems/synthetic biology applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available