Domain trigger interaction

Binding of the ligand of the Fas receptor triggers clustering of the receptor and association of the cofactor FADD (fas-assodated protein with death domain) which interacts with the receptor via its death domain (DD). Procaspase 8 binds to FADD via a common DED (death effector domain) motif and is thereby also recruited into the Fas-receptor associated complex. Due to the clustering of the proteins, proximity-induced cleavage of procaspase 8 to the mature initiator caspase 8 takes place. This activates the effector caspases and triggers cell death. 

In the one-dimensional NMR experiments discussed earlier, the FID was recorded immediately after the pulse, and the only time domain involved (ij) was the one in which the FID was obtained. If, however, the signal is not recorded immediately after the pulse but a certain time interval (time interval (the evolution period) the nuclei can be made to interact with each other in various ways, depending on the pulse sequences applied. Introduction of this second dimension in NMR spectroscopy, triggered byjeener s original experiment, has resulted in tremendous advances in NMR spectroscopy and in the development of a multitude of powerful NMR techniques for structure elucidation of complex organic molecules. 

Activation of the caspases requires the help of a number of cofactors that are also known as activators or adaptors. Different cofactors are involved depending on the trigger mechanism of caspase activation. A central function of the cofactors is to bring about aggregation and thus activation of the procaspases. This occurs by specific protein-protein interactions with the help of common structural motives. Examples of such motives are the death domains (DD), death effector domains (DED) and the caspase recruitment domains (CARD), which all have a similar structure of six a-heh-ces. 

Many of the signaling protein kinases, including PKA, PKC, PKG, and members of the MAPK cascade, phosphorylate Ser or Thr residues in their target proteins, which in some cases acquire the ability to interact with partner proteins through the phosphorylated residue, triggering a downstream process. An alphabet soup of domains that bind (P)-Ser or (P)-Thr residues has been identified, and more are sure to be found. Each domain favors a certain sequence around the phosphorylated residue, so the domains represent families of highly specific recognition sites, able to bind to a specific subset of phosphorylated proteins. 

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