Signal peptide discrimination

Signal peptide identification, like DNA intron/exon sequence discrimination, involves the two related problems of signal peptide discrimination (search for content) and cleavage site recognition (search for signal). It is well suited to neural network methods for several reasons. The functional units are encoded by local, linear sequences of amino acids rather than global 3-dimensional structures (Claros et al., 1997). The ambiguity of... 

Since signal peptides are the most obvious discriminating feature of secretory proteins, and SecB is a component of the secretion machinery, it would seem likely that the signal peptide is the principal site for SecB interaction. Indeed, several lines of evidence support this idea. 

Petersen TN, Brunak S, von Heijne G, et al. SignalP 4.0 discriminating signal peptides from transmembrane regions. Nat Methods. 2011 8 785-6. doi 10.1038/nmeth.l701. 

A cross-reactive sensor array based on luminescence changes has been reported by Severin and coworkers [74]. In this case no synthetic modifications were operated, but the sensing elements were created by mixing some metal complexes with fluorescent dyes. The complex formation between metal ions, such as Rh, Ru or Pd, quenches the dye fluorescence the peptide competes with the dye for metal ion complexation, removing it from the complex. The fluorescence turn on is the signal of the peptide interaction. The activation of fluorescence is also an indication of the equilibrium reported in Fig. 24 and it is the basis of the peptides discrimination. The sensor array was able to differentiate between several dipeptides at 20-50 X 10 M concentration higher oligopeptides, such as bradykinin and kallidin were also discriminated and the system was also able to differentiate between two dipeptides, carnosine and homocamosine, in a more complex environment such as human serum. 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

This rationale led Severin et alP to construct an array consisting of CuCh, NiCh, and three UV-active chro-mophores, resulting in six metal-indicator combinations to comprise a dynamic combinatorial library. A dynamic combinatorial library is an array of differential sensors that are simultaneously present in one solution, under thermodynamic control, such that this one solution can provide multiple signals from the composite interactions of an analyte with all the sensors in solution. They found that this simple dynamic combinatorial library of receptors was able to successfully discriminate two angiotensin peptides (angiotensin I and angiotensin II) and mixtures of these two peptides. 

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