Targeting signal

O neill LA (2006) Targeting signal transduction as a strategy to treat inflammatory diseases. Nat Rev Drug Discov 5 549-563... 

Cleavage occur s at the scissile bond. Residues in the substrate towards the N-terminus are numbered PI, P2, P3, etc, whereas residues towards the C-terminus are numbered PI, P2, P3 etc. Cleavage occurs between PI and P1. For a peptidase with limited specificity, only the residue in PI or PI is important for specificity. A peptidase with an extended substrate binding site will have a preference for residues in other positions. For example cathepsin L prefers substrates with phenylalanine in P2 and arginine in PI. However, this is a preference only, and cathepsin L cleaves substrates after other amino acids. Caspase-3 has a preference for Asp in both P4 and PI, but it is unusual for substrate specificity to extend much further from the scissile bond. The peptidase with the most extended substrate specificity may be mitochondrial intermediate peptidase that removes an octopeptide targeting signal from the N-terminus of cytoplasmically synthesized proteins that are destined for import into the mitochondrial lumen. 

Muller G (2000) Peptidomimetic SH2 Domain Antagonists for Targeting Signal Transduction. 211 17-59... 

Antigens Type of antibodies Indications Transformed plant Promoter Targeting signal Expression Refer- ences... 

Zearalenone (mycotoxin) scFv Passive immunization of animals in their feed A. thaliana (ecotype Columbia) Inducible lac No targeting signal - 58... 

Francesconi, A. and Duvoisin, R. (2002) Alternative splicing unmasks dendritic and axonal targeting signals in metabotropic glutamate receptor 1. J. Neurosci. 22, 2196-2205. 

Using the bi-static concept can reduce all of the above mentioned problems. The spatial separation of the transmitter and receiver antennas leads to significant attenuation of the direct path signal. In addition, the near-far target problem is reduced, while the target signal can be... 

But in real radar applications the average noise and clutter power level (/x) is unknown and must be estimated in the detection procedure first. This is done by several published CFAR procedures, which will be discussed in this section, where each specific CFAR technique is motivated by assumptions about a specific background signal or target signal model. 

Prediction of mitochondrial targeting signals is not an easy task. The proposed amphiphilic nature is not clear enough. Nakai and Kanehisa (1992) developed a simple method based on the amino acid composition of the segment of most amino-terminal 20 residues. In addition, a simple rule to discriminate the bipartite signal of intermembrane-space proteins was also included in PSORT. 

Fujiwara et al. (1997) proposed an HMM that can detect mitochondrial targeting signals. The HMM was automatically created to best explain the training data. Although it could model the signals in the training data, further analysis using more data is desirable because the model has many numeric parameters. 

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