Tachyplesin I (TPI) is an antimicrobial polypeptide originally detected in Japanese Horse Shoe Crab. The antimicrobial activity of the peptide is closely related to the composition of the pathogen membrane and ability of the peptide to permeabilize the cell membranes. Bacteria and fungi have negatively charged membranes, and the interaction of cationic peptides such as tachyplesin I is mediated in large part by electrostatic interactions[1] (you can see the Hydrophobic and Polar amino acids). It shows high affinity for lipopolysaccharides (LPS) of gram-negative bacteria, thus neutralizing its effects. It has also been reported to inhibit the growth of gram positive bacteria, fungui and viruses.
Structural highlightsThe amino acid sequence of the TPI is NH₂-Lys-Trp-Cys-Phe-Arg-Val-Cys-Tyr-Arg-Gly-Ile-Cys-Tyr-Arg-Arg-Cys-Arg-CONH₂. It adopts antiparallel β-sheet (hairpin) conformation in solution stabilized by two cross-strand disulfide bonds between Cys³-Cys¹⁶ and Cys⁷-Cys¹², and its C-terminus is amidated.[1][2] Tachyplesin is highly stable at low pH and high temperature. This stability seems to be due to the rigid structure imposed by the two disulfid linkage.[3] Besides, there exists H-bond and aromatic ring stacking interactions which helps stabilizing the hairpin loop structure of the peptide. There are three linear derivatives of TPI: TPY4, TPF4 and TPA4. File:Derivatives.jpg Since linear tachyplesin analogues do not show preferential affinity for LPS, the hairpin properties of the peptide seems to be important for recognition of lipopolysaccharides and its biological activities. TPI undergoes confirmation change in presence of LPS . The backbone of the polypeptide becomes more rigid and twisted in presence of LPS, than in the presence of water , making it more stable. Mode of actionTPI can bind to LPS and also has ability to permeabilize the cell membrane of pathogens. Docking model suggests strong affinity to LPS gained by interaction between cationic residues of TPI with phosphate group and sachharides of LPS. Furthermore, interaction between hydrophobic residues of TPI with acyl chains of LPS strengthens the TPI/LPS interaction. The binding of TPI to LPS neutralizes LPS, which is widely considered as endotoxin. In addition to LPS binding, footpriting analysis has revealed the binding of TPI to DNA by interacting specifically in minor groove of DNA duplex. The interaction between TPI and DNA is contributed by secondary structure of the peptide which contains an antiparallel beta-sheet constrained by two disulfide bridges and connected by β-turn. Importance and relevanceEvidences suggest that TPI has ability to permeabilize the cell membranes of pathogens.[1]. Also, LPS and DNA being the potential biological targets of the peptide, its antimicrobial activity might be exploited. Eyeing the potential of TPI, it has been insetred successfully in genome of Ornithogalum dubium and Ornithogalum thyrsoides. These ornamentals plants were originally sensitive to soft rot erwinias (SREs) and insertion of TPI in the plants has successfully protected them without affecting their normal physiology. FunctionThis is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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Shulamit Idzikowski, Janak Raj Joshi, Michal Harel, Angel Herraez, Alexander Berchansky, Jaime Prilusky, Joel L. Sussman
This page was last modified 14:43, 29 December 2014.
