Degron

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A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. A degron sequence can occur at either the N or C-terminal region, these are called N-Degrons or C-degrons respectively.

A temperature sensitive degron takes advantage of the N-end rule pathway, in which a destabilizing N-terminal residue dramatically decreases the in vivo half-life of a protein.[1] The degron is a fusion protein of ubiquitin, arginine, and DHFR. DHFR is dihydrofolate reductase, a mouse-derived enzyme that functions in the synthesis of thymine. It is also heat-labile - at a higher temperature of 37°C, becomes slightly unfolded and exposes an internal lysine, the site of poly-ubiquitination. Proteolysis is highly processive, and the protein is degraded by the proteasome. The degron can be fused to a gene to produce the corresponding temperature-sensitive protein. It is portable, and can be transferred on a plasmid.

A ligand controllable degron takes advantage of a mutant form of FKBP12 protein that can be controlled using a synthetic ligand.[2] Small molecule Shield1 binds specifically to the degron making it inactive. An inactive degron no longer promotes protein degradation. The degron is reactivated when the small molecule is removed by washing the cells and active protein degradation occurs through proteasome mediated proteolysis.[3]

References[edit]

  1. ^ Dohmen, R.J., P. Wu, and A. Varshavsky, Heat-inducible degron: a method for constructing temperature-sensitive mutants. Science, 1994. 263(5151): p. 1273-1276.
  2. ^ Schoeber JP, van de Graaf SF, Lee KP, Wittgen HG, Hoenderop JG, Bindels RJ,Conditional fast expression and function of multimeric TRPV5 channels using Shield-1.Am J Physiol Renal Physiol. 2009 Jan;296(1):F204-11
  3. ^ Chu BW, Banaszynski LA, Chen LC, Wandless TJ,Recent progress with FKBP-derived destabilizing domains,Bioorg Med Chem Lett. 2008 Nov 15;18(22):5941-4

See also[edit]