Department of Chemical and Systems Biology, Stanford University, CA, United States.
Bioorg Med Chem Lett. 2011 Sep 1;21(17):4965-8. doi: 10.1016/j.bmcl.2011.06.006. Epub 2011 Jun 16.
Two orthogonal destabilizing domains have been developed based on mutants of human FKBP12 as well as bacterial DHFR and these engineered domains have been used to control protein concentration in a variety of contexts in vitro and in vivo. FKBP12 based destabilizing domains cannot be rescued in the yeast Saccharomyces cerevisiae; ecDHFR based destabilizing domains are not degraded as efficiently in S. cerevisiae as in mammalian cells or Plasmodium, but provide a starting point for the development of domains with increased signal-to-noise in S. cerevisiae.
已经开发了两种基于人 FKBP12 突变体以及细菌 DHFR 的正交去稳定结构域，并且这些工程化的结构域已被用于在体外和体内的各种情况下控制蛋白质浓度。基于 FKBP12 的去稳定结构域不能在酵母酿酒酵母中恢复；基于 ecDHFR 的去稳定结构域在酿酒酵母中的降解效率不如在哺乳动物细胞或疟原虫中高，但为在酿酒酵母中开发具有更高信号噪声比的结构域提供了起点。
