Peptide leader

Species Strain Protein leader peptide type no. 

Species Strain Gene/ Protein No. of amino acids including N-terminal leader peptide/N-terminal leader peptide Lattice type GenBank accession no. 

Human serum albumin CaMVenhanced 35S promoter/ A1MV RNA synthetic leader sequence/nos terminator Native or PR-S leader peptide S. tuberosum (leaves) 0.02% ofTSP 48... 

Howe, C., and Wallace, T. (1990). Prediction of leader peptide cleavage sites for polypeptides of the thylakoid lumen. Nucl. Acids Res. 18, 3417-3417. 

The site of synthesis of numerous proteins is remote from their site of function. During transfer from one site to the other, proteins must, therefore, cross cellular membranes [43] [44], Proteins are usually synthesized as precursors containing an amino terminal extension, called the signal (leader) peptide, the sequence of which contains the necessary information to guide the protein to and across a specific membrane. After transmembrane transport (called translocation), the signal peptide is cleaved off by specific signal peptidases, which are found in the rough endoplasmic reticulum, and the... 

D Souza GG, Boddapati S, Lightowlers RN, Weissig V. Mitochondriotropic vesicles deliver mitochondrial leader peptide conjugates of circular and linear double-stranded DNA into mammalian mitochondria. Proc Inti S5unp Control Rel Bioact Mater 2005 32. 

Figure 4 The biosynthesis of nisin A as a representative example of the posttranslational maturation process of lantibiotics. Following ribosomal synthesis, NisB dehydrates serine and threonine residues in the structural region of the prepeptide NisA. NisC subsequently catalyzes intramolecular addition of cysteine residues onto the dehydro amino acids in a stereo- and regioselective manner. Subsequent transport of the final product across the cell membrane by NisT and proteolytic cleavage of the leader sequence by NisP produces the mature lantibiotic. For the sequence of the leader peptide, see Figure 6. Adapted with permission from J. M. Willey W. A. van der Donk, Annu. Rev. Microbiol. 2007, 61, 477-501.

An alternative classification scheme was introduced in 2002 and this divides lantibiotics into two subgroups, class I and class II. This scheme primarily classifies lantibiotics according to their biosynthetic enzymes and sequence homology of their leader peptides. Similar to most biosynthetic pathways in bacteria, the genes for lantibiotic biosynthesis are clustered. They have been designated the generic locus symbol Ian, with a more... 

Figure 5 The structural region of the NisA prepeptide is modified by a putative muitienzyme compiex consisting of the dehydratase NisB, the cyclase NisC, and the transporter NisT. After export, the leader peptide is removed by NisP, which is anchored to the cell wall. Mature nisin activates the two-component response regulatory system NisRK, and phosphorylated NisR serves as a positive regulator of nisA and the biosynthetic and immunity operons expressing NisABTC and NisFEG,...

Of the various MutA leader peptide mutations generated in vivo, only Leu—7Lys and He—4Asp fully disrupted mutacin II biosynthesis, but it could not be determined what step(s) in the overall maturation process had been perturbed. Recent in vitro studies with mutants of LctA at Leu—7 showed that incorporation of any charged residue strongly perturbed lacticin 481 synthetase activity whereas the Leu—7Ala mutant was still... 

Figure 7 Sequence requirements of the leader peptides of nisin, mutacin II, lacticin 481, and lacticin 3147 as determined by site-directed mutagenesis. For nisin and mutacin II, mutants that still resulted in full processing of the prepeptides are shown in green, whereas mutants that resulted in abolished lantibiotic production are shown in orange. For lacticin 481, the mutants shown in green were good substrates in vitro for either the bifunctional synthetase LctM or the protease domain of LctT, whereas the mutants in orange were poor substrates. Conserved residues in the leader peptides of subgroups of lantibiotics are indicated in blue and red as described in Figure 6.

The current hypothesis for the role of the leader peptide in dehydratase activity and processivity is shown in Figure 8 and is based on the results from several studies. LctM is proposed to recognize a certain secondary structure, possibly helical (see Section 5.08.3.2), adopted by the C-terminal segment of the leader peptide. Leader peptide binding is then postulated to bring the structural region of the substrate in close proximity to... 

Figure 8 The proposed role of the leader peptide in LctM activity. Leader peptide binding is proposed to shift the equilibrium between inactive and active enzyme toward the latter. Reprinted with permission from G. C. Patton M. Paul L. E. Cooper C. Chatterjee, W. A. van der Donk, Biochemistry 2008, 47, 7342-7351.

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