DETERMINANTS OF SPECIFICITY AND PROMISCUITY WITHIN THE BH3 BINDING RECEPTORS INVOLVED IN PROGRAMED CELL DEATH

Kevin Carlson , Sean Campbell, Indraneel Ghosh

DETERMINANTS OF SPECIFICITY AND PROMISCUITY WITHIN THE BH3 BINDING RECEPTORS INVOLVED IN PROGRAMED CELL DEATH

The BCL-2 homology proteins govern the intrinsic pathway of apoptosis. This homology includes apoptotic and anti-apoptotic proteins whose interactions determine weather a cell lives or dies. Past research has focused on the effect of smaller BH3 only proteins on the homology. Using in-vitro translation and a luciferase based florescence assay we have examined the effects of mutations to the receptor pocket of BCL-XL on interactions with 9 BH3 only proteins. This assay has identified the importance of the mutant R139A. This mutation selectively increases binding to the Bad-BH3 peptide while disrupting interactions with the other helices.  These results were confirmed through CD, FPLC, and ITC. This work is currently being extended to other members of the BCL-2 homology. 

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