Difference between revisions of "Team:BostonU/Modeling/Dimerization Domain"
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| + | <h3>Dimerization Domains</h3> | ||
| + | <p>In our project we explored the three different conditional dimerization domain pairs: FKBP and FRB domains induced by the small molecule Rapalog, ABI and PYL domains induced by the small molecule Abscisic Acid, and CRY2 and CIBN domains induced by blue light stimulus. We looked into three systems because each had its own advantages. We hypothesized that these different domains would give different levels of protein activity control. Additionally, each of these systems is orthogonal, so theoretically multiple conditionally-dimerized proteins could be controlled in the same cell.</p> | ||
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| + | <h3>FKBP/FRB/Rapalog</h3> | ||
| + | <p>This conditional dimerization system is the most widely studied in the literature. The two protein domains are the smallest pair of the three that we investigated, and we hypothesized that smaller domains would be advantageous because they might have the least interference with folding of the independent split halves and overall protein activity when dimerized. In addition, FKBP and FRB bind very tightly in the presence of rapalog, which means that only a small amount of inducer needs to be administered to induce dimerization. One disadvantage of this system is that FKBP and FRB do not easily come apart after dimerization is induced. This could be troublesome for applications in which protein activity needs to be rapidly modulated. Additionally, Rapalog does have some off target effects in mammalian cells, which could be potentially troublesome for <i>in vivo</i> applications.</p> | ||
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Revision as of 01:58, 18 September 2015
| Modeling | Dimerization Domains | Experimental Workflow |
Dimerization Domains
In our project we explored the three different conditional dimerization domain pairs: FKBP and FRB domains induced by the small molecule Rapalog, ABI and PYL domains induced by the small molecule Abscisic Acid, and CRY2 and CIBN domains induced by blue light stimulus. We looked into three systems because each had its own advantages. We hypothesized that these different domains would give different levels of protein activity control. Additionally, each of these systems is orthogonal, so theoretically multiple conditionally-dimerized proteins could be controlled in the same cell.
FKBP/FRB/Rapalog
This conditional dimerization system is the most widely studied in the literature. The two protein domains are the smallest pair of the three that we investigated, and we hypothesized that smaller domains would be advantageous because they might have the least interference with folding of the independent split halves and overall protein activity when dimerized. In addition, FKBP and FRB bind very tightly in the presence of rapalog, which means that only a small amount of inducer needs to be administered to induce dimerization. One disadvantage of this system is that FKBP and FRB do not easily come apart after dimerization is induced. This could be troublesome for applications in which protein activity needs to be rapidly modulated. Additionally, Rapalog does have some off target effects in mammalian cells, which could be potentially troublesome for in vivo applications.