Role of the Leader Peptide

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.

Chakicberlp A, Hansen JN. Role of the leader and structural ri ions of prelantibiotic peptides as assessed by expressing nisin-subtilin chimeras in Bodllus subrilis 168, and characterization of their physical, chemical, and antimicrobial properties, J Biol Chem 1995 270 23533-23539. 

Fig. 8. A conceptual maturation pathway for nisin is given as a 5-step process [40]. A two-component signal transduction system induces transcription (step 1). Translation results in an inactive unmodified precursor peptide (step 2). The leader peptide is proposed to play a role in targeting of the precursor to a membrane-located modification complex (step 3). Dehydration and lanthionine and dehydro-lanthionine formation (step 4) is followed by extracellular processing and secretion (step 5)... 

TrpR, which is a DNA binding repressor protein, regulates transcription initiation of the E. coli trpEDCBA operon. Under tryptophan limiting conditions, TrpR represses transcription initiation, whereas repression is relieved in the presence of excess tryptophan. Once transcription initiates the elongating transcription complex is subject to control by transcription attenuation (reviewed in References 5 and 6). The leader transcript can form three RNA secondary structures that are referred to as the pause hairpin, the antiterminator structure, and an intrinsic terminator hairpin. Because the antiterminator shares nucleotides in common with the terminator, their formation is mutually exclusive. The pause hairpin has two additional roles in this transcription attenuation mechanism it serves as an anti-antiterminator stmc-ture that prevents antiterminator formation, and it codes for a leader peptide. A model of the E. coli trp operon transcription attenuation mechanism is presented in Fig. 2a. 

In addition, a leader peptide encoded by the opd gene functions to insert the processed parathion hydrolase protein in the membrane of the native Flavobacterium and Pseudomonas diminuta strains but causes the protein to be excreted by Streptomyces lividans (26,28). The ability of these regulatory elements to function across such a wide range of microorganisms is strongly suggestive of the important role that plasmid mobility and recombination have played in the dissemination of the opd gene. 

---