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| 선택 | Cat.No. | 제품명 | 가격(VAT별도) | 수량 |
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제품특징
The iDimerize Reverse Dimerization System brings the disruption of protein complexes under real-time, small molecule control. A protein of interest is fused to the DmrD binding domain, and the fusion protein molecules aggregate unless the D/D Solubilizer ligand is present. Reverse Dimerization: Disrupting Protein-Protein InteractionsThe iDimerize Reverse Dimerization System is a "reverse dimerization" system-aggregation is the resting state, and the D/D Solubilizer breaks up protein-protein interactions. Therefore, the iDimerize Reverse Dimerization System complements inducible dimerization, and can be used in analogous ways to createinducible alleles. In principle, most processes that can be brought under dimerizer control can also be controlled in the reverse manner using this kit to turn off a process that is activated by oligomerization.
Figure 1. Mechanism of the iDimerize Reverse Dimerization System. The Reverse Dimerization System incorporates a binding motif (purple) that causes protein aggregation and a dimerizer (yellow) which can be used to disaggregate (solubilize) the proteins. This system can be used to study intracellular transport and to induce regulated secretion.
□ Inducible Secretion
The ability to create large protein aggregates has unique applications. For example, adding a secretory signal sequence to fusion proteins allows them to be reversibly stored as aggregates in the endoplasmic reticulum. The ligand can then be added to induce a rapid pulse of protein secretion from the cells. This method has been used to induce rapid, transient and tightly-regulated secretion of human growth hormone (hGH) and insulin (1). Protein aggregates can also be used in protein trafficking research. For example, this approach has been used to discover the existence of "mega-vesicles" transporting cargo across the Golgi stack (2).
Figure 2. The iDimerize Reverse Dimerization System enables dose-dependent control of protein secretion. Fusion proteins containing DmrD domains localize to the endoplasmic reticulum as massive aggregates (left). When the D/D Solubilizer is added, it dissolves the aggregates and allows the protein to be exported through the secretory apparatus (right). To ensure secretion of the authentic protein, a furin cleavage site is positioned between the DmrD domains and the protein of interest. Since furin is exclusively expressed in the trans Golgi, the fusion protein will be processed as it traverses this compartment,resulting in the secretion of the correctly processed protein.
□ D/D Solubilizer Ligand
The D/D Solubilizer is a synthetic, cell-permeable ligand that can be used to disrupt dimerization of fusion proteins containing the DmrD domain. The D/D Homodimerizer has been tested in vitro and in mice. It is nontoxic. We suggest testing various D/D Homodimerizer concentrations within the recommended range (10-500 nM) for different lengths of time (30 minutes to 12+ hours) in order to obtain a complete dose-response profile. The D/D Solubilizer performs the same function as the AP21998 ligand, which was previously supplied by ARIAD Pharmaceuticals Inc. It is a different molecule than AP21998.
□ Applications
● Rapid, reversible changes in the subcellular location, aggregation state and/or biological activity of engineered
proteins, in vitro or in vivo
● Rapid induction of protein secretion
● Protein trafficking studies
● Inducible animal models and cell lines
□ References
1.Rivera, V. M., et al. (2000) Science 287(5454):826-830. Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. 2.Volchuk, A., et al. (2000) Cell 102(3):335-348. Megavesicles implicated in the rapid transport of intracisternal aggregates across the Golgi stack.
