Evaluation of leader peptides that affect the secretory ability of a multiple bacteriocin transporter, EnkT

2018 ◽  
Vol 126 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Hirotoshi Sushida ◽  
Naoki Ishibashi ◽  
Takeshi Zendo ◽  
Pongtep Wilaipun ◽  
Vichien Leelawatcharamas ◽  
...  
Keyword(s):  
Leader Peptides

scholarly journals Genomic organization of the mouse granzyme A gene. Two mRNAs encode the same mature granzyme A with different leader peptides.

1992 ◽  
Vol 267 (35) ◽  
pp. 25488-25493
Author(s):  
R.J. Hershberger ◽  
H.K. Gershenfeld ◽  
I.L. Weissman ◽  
L Su
Keyword(s):  
Genomic Organization ◽  
Granzyme A ◽  
Leader Peptides

scholarly journals The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects

2009 ◽  
Vol 207 (1) ◽  
pp. 207-221 ◽  
Author(s):  
Cláudia C. Oliveira ◽  
Peter A. van Veelen ◽  
Bianca Querido ◽  
Arnoud de Ru ◽  
Marjolein Sluijter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Antigen Processing ◽  
Germ Line ◽  
Wide Spectrum ◽  
Cell Subset ◽  
Target Cells ◽  
Peptide Epitopes ◽  
Leader Peptides

The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b–restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells.

scholarly journals Follow the leader: the use of leader peptides to guide natural product biosynthesis

2009 ◽  
Vol 6 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Trent J Oman ◽  
Wilfred A van der Donk
Keyword(s):  
Natural Product ◽  
Natural Product Biosynthesis ◽  
Leader Peptides

scholarly journals Molecular and Evolutionary Analysis ofBorrelia burgdorferi 297 Circular Plasmid-Encoded Lipoproteins with OspE- and OspF-Like Leader Peptides

1999 ◽  
Vol 67 (3) ◽  
pp. 1526-1532 ◽  
Author(s):  
Darrin R. Akins ◽  
Melissa J. Caimano ◽  
Xiaofeng Yang ◽  
Felix Cerna ◽  
Michael V. Norgard ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Gene Fusion ◽  
Evolutionary Analysis ◽  
Hypervariable Regions ◽  
Leader Peptides ◽  
N Terminus ◽  
Generating Sequence ◽  
Flanking Regions ◽  
Encoding Genes ◽  
Sequence Similarities

ABSTRACT We previously described two OspE and three OspF homologs inBorrelia burgdorferi 297 (D. R. Akins, S. F. Porcella, T. G. Popova, D. Shevchenko, S. I. Baker, M. Li, M. V. Norgard, and J. D. Radolf, Mol. Microbiol. 18:507–520, 1995; D. R. Akins, K. W. Bourell, M. J. Caimano, M. V. Norgard, and J. D. Radolf, J. Clin. Investig. 101:2240–2250, 1998). In this study, we characterized four additional lipoproteins with OspE/F-like leader peptides (Elps) and demonstrated that all are encoded on plasmids homologous to cp32 and cp18 from the B31 and N40 strains, respectively. Statistical analysis of sequence similarities using the binary comparison algorithm revealed that the nine lipoproteins from strain 297, as well as the OspE, OspF, and Erp proteins from the N40 and B31 strains, fall into three distinct families. Based upon the observation that these lipoproteins all contain highly conserved leader peptides, we now propose that the ancestors of each of the three families arose from gene fusion events which joined a common N terminus to unrelated proteins. Additionally, further sequence analysis of the strain 297 circular plasmids revealed that rearrangements appear to have played an important role in generating sequence diversity among the members of these three families and that recombinational events in the downstream flanking regions appear to have occurred independently of those within the lipoprotein-encoding genes. The association of hypervariable regions with genes which are differentially expressed and/or subject to immunological pressures suggests that the Lyme disease spirochete has exploited recombinatorial processes to foster its parasitic strategy and enhance its immunoevasiveness.

scholarly journals Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides in Escherichia coli

2018 ◽  
Vol 140 (38) ◽  
pp. 11884-11888 ◽  
Author(s):  
Tong Si ◽  
Qiqi Tian ◽  
Yuhao Min ◽  
Linzixuan Zhang ◽  
Jonathan V. Sweedler ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Rapid Screening ◽  
Leader Peptides

scholarly journals High-Yield Intra- and Extracellular Protein Production Using Bacillus megaterium

2010 ◽  
Vol 76 (12) ◽  
pp. 4037-4046 ◽  
Author(s):  
Simon Stammen ◽  
Britta Katrin Müller ◽  
Claudia Korneli ◽  
Rebekka Biedendieck ◽  
Martin Gamer ◽  
...  
Keyword(s):  
Bacillus Megaterium ◽  
Protein Production ◽  
Expression System ◽  
Protein Export ◽  
Extracellular Protein ◽  
High Yield ◽  
Leader Peptide ◽  
Leader Peptides ◽  
Extracellular Protein Production ◽  
Dependent Protein

ABSTRACT The Bacillus megaterium protein production system based on the inducible promoter of the xyl operon (P xylA ) was systematically optimized. Multiple changes in basic promoter elements, such as the −10 and −35 region and the ribosome-binding site, resulted in an 18-fold increase of protein production compared to the production of the previously established system. The production in shaking-flask culture of green fluorescent protein (Gfp) as a model product led to 82.5 mg per g cell dry weight (gCDW) or 124 mg liter−1. In fed-batch cultivation, the volumetric protein yield was increased 10-fold to 1.25 g liter−1, corresponding to 36.8 mg protein per gCDW. Furthermore, novel signal peptides for Sec-dependent protein secretion were predicted in silico using the B. megaterium genome. Subsequently, leader peptides of Vpr, NprM, YngK, YocH, and a computationally designed artificial peptide were analyzed experimentally for their potential to facilitate the secretion of the heterologous model protein Thermobifida fusca hydrolase (Tfh). The best extracellular protein production, 5,000 to 6,200 U liter−1 (5.3 to 6.6 mg liter−1), was observed for strains where the Tfh export was facilitated by a codon-optimized leader peptide of YngK and by the signal peptide of YocH. Further increases in extracellular protein production were achieved when leader peptides were used in combination with the optimized expression system. In this case, the greatest extracellular enzyme amount of 7,200 U liter−1, 7.7 mg liter−1, was achieved by YocH leader peptide-mediated protein export. Nevertheless, the observed principal limitations in protein export might be related to components of the Sec-dependent protein transport system.

scholarly journals Qa-1b Binds Conserved Class I Leader Peptides Derived from Several Mammalian Species

1998 ◽  
Vol 188 (5) ◽  
pp. 973-978 ◽  
Author(s):  
Zoran Kurepa ◽  
Charles A. Hasemann ◽  
James Forman
Keyword(s):  
Surface Plasmon Resonance ◽  
Signal Sequence ◽  
Mammalian Species ◽  
Class I ◽  
Mammalian Evolution ◽  
Human Class ◽  
Leukocyte Antigen ◽  
High Affinity ◽  
Leader Peptides ◽  
Almost All

Qa-1b binds a peptide (AMAPRTLLL), referred to as Qdm (for Qa-1 determinant modifier), derived from the signal sequence of murine class Ia molecules. This peptide binds with high affinity and accounts for almost all of the peptides associated with this molecule. Human histocompatibility leukocyte antigen (HLA)-E, a homologue of Qa-1b, binds similar peptides derived from human class Ia molecules and interacts with CD94/NKG2 receptors on natural killer cells. We used surface plasmon resonance to determine the ability of Qa-1b to bind related ligands representing peptides derived from the leaders of class I molecules from several mammalian species. All of the peptides reported to bind HLA-E bound readily to Qa-1b. In addition, peptides derived from leader segments of different mammals also bound to Qa-1b, indicating a conservation of this “Qdm-like” epitope throughout mammalian evolution. We have attempted to define a minimal peptide on a polyglycine backbone that binds Qa-1b. Our previous findings showed that P2 and P9 are important but not sufficient for binding to Qa-1b. Although a minimum peptide (GMGGGGLLL) bound Qa-1b, its interaction was relatively weak, as were peptides sharing five or six residues with Qdm, indicating that multiple native residues are required for a strong interaction. This finding is consistent with the observation that this molecule preferentially binds this single ligand.

scholarly journals Zn-dependent bifunctional proteases are responsible for leader peptide processing of class III lanthipeptides

2019 ◽  
Vol 116 (7) ◽  
pp. 2533-2538 ◽  
Author(s):  
Shaoming Chen ◽  
Bing Xu ◽  
Erquan Chen ◽  
Jiaqi Wang ◽  
Jingxia Lu ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Leader Peptide ◽  
Biosynthetic Gene ◽  
Class Iii ◽  
Biosynthetic Gene Clusters ◽  
Peptide Processing ◽  
Leader Peptides ◽  
Biochemical Studies ◽  
Modified Peptides

Lanthipeptides are an important subfamily of ribosomally synthesized and posttranslationally modified peptides, and the removal of their N-terminal leader peptides by a designated protease(s) is a key step during maturation. Whereas proteases for class I and II lanthipeptides are well-characterized, the identity of the protease(s) responsible for class III leader processing remains unclear. Herein, we report that the class III lanthipeptide NAI-112 employs a bifunctional Zn-dependent protease, AplP, with both endo- and aminopeptidase activities to complete leader peptide removal, which is unprecedented in the biosynthesis of lanthipeptides. AplP displays a broad substrate scope in vitro by processing a number of class III leader peptides. Furthermore, our studies reveal that AplP-like proteases exist in the genomes of all class III lanthipeptide-producing strains but are usually located outside the biosynthetic gene clusters. Biochemical studies show that AplP-like proteases are universally responsible for the leader removal of the corresponding lanthipeptides. In addition, AplP-like proteases are phylogenetically correlated with aminopeptidase N from Escherichia coli, and might employ a single active site to catalyze both endo- and aminopeptidyl hydrolysis. These findings solve the long-standing question as to the mechanism of leader peptide processing during class III lanthipeptide biosynthesis, and pave the way for the production and bioengineering of this class of natural products.

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