Tachyplesin
From Proteopedia
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== Introduction == | == Introduction == | ||
<StructureSection load='1MA2' size='340' side='right' caption='1MA2' scene='67/671725/First_scene/1'> | <StructureSection load='1MA2' size='340' side='right' caption='1MA2' scene='67/671725/First_scene/1'> | ||
| - | Tachyplesin | + | Tachyplesin 1 (TP-1) is an [http://en.wikipedia.org/wiki/Antimicrobial_peptides antimicrobial polypeptide] originally detected in the leukocytes of Japanese [http://en.wikipedia.org/wiki/Horseshoe_crab 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 <scene name='67/671725/Cationic_peptide_tpi/1'>cationic peptides such as | + | 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 <scene name='67/671725/Cationic_peptide_tpi/1'>cationic peptides such as TP-1 </scene> is mediated in large part by electrostatic interactions<ref name=Laederach>PMID:12369825</ref> (you can see the {{Template:ColorKey_Hydrophobic}} and {{Template:ColorKey_Polar}} amino acids). |
It shows high affinity for [http://en.wikipedia.org/wiki/Lipopolysaccharide lipopolysaccharides (LPS)] of [http://en.wikipedia.org/wiki/Gram-negative_bacteria gram-negative bacteria], thus neutralizing its effects. It has also been reported to inhibit the growth of [http://en.wikipedia.org/wiki/Gram-positive_bacteria gram positive bacteria], [http://en.wikipedia.org/wiki/Fungus fungui] and [http://en.wikipedia.org/wiki/Virus viruses]. | It shows high affinity for [http://en.wikipedia.org/wiki/Lipopolysaccharide lipopolysaccharides (LPS)] of [http://en.wikipedia.org/wiki/Gram-negative_bacteria gram-negative bacteria], thus neutralizing its effects. It has also been reported to inhibit the growth of [http://en.wikipedia.org/wiki/Gram-positive_bacteria gram positive bacteria], [http://en.wikipedia.org/wiki/Fungus fungui] and [http://en.wikipedia.org/wiki/Virus viruses]. | ||
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== Structural highlights == | == Structural highlights == | ||
| - | Tachyplesine | + | Tachyplesine 1 is a 17-residue peptide containing six cationic residues. |
It's molecular weight is 2,269 and has pI of 9.93. <ref name=Chen>Chen, Yixin, et al. "RGD-Tachyplesin inhibits tumor growth." Cancer research 61.6 (2001): 2434-2438.</ref> | It's molecular weight is 2,269 and has pI of 9.93. <ref name=Chen>Chen, Yixin, et al. "RGD-Tachyplesin inhibits tumor growth." Cancer research 61.6 (2001): 2434-2438.</ref> | ||
| - | The amino acid sequence of the | + | The amino acid sequence of the TP-1 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 <scene name='67/671725/Disulfide_bonds/1'> disulfide bonds </scene> between Cys³-Cys¹⁶ and Cys⁷-Cys¹², and its [http://en.wikipedia.org/wiki/Protein_primary_structure C-terminus is amidated].<ref name=Laederach>PMID:12369825</ref><ref name=Kushibiki>PMID:24389234</ref> | It adopts antiparallel β-sheet (hairpin) conformation in solution stabilized by two cross-strand <scene name='67/671725/Disulfide_bonds/1'> disulfide bonds </scene> between Cys³-Cys¹⁶ and Cys⁷-Cys¹², and its [http://en.wikipedia.org/wiki/Protein_primary_structure C-terminus is amidated].<ref name=Laederach>PMID:12369825</ref><ref name=Kushibiki>PMID:24389234</ref> | ||
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| - | 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.<ref name=Nakamura>Nakamura, Takanori, et al. "Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure." Journal of Biological Chemistry 263.32 (1988): 16709-16713</ref> | + | Tachyplesin 1 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.<ref name=Nakamura>Nakamura, Takanori, et al. "Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure." Journal of Biological Chemistry 263.32 (1988): 16709-16713</ref> |
Besides, there exists H-bond and aromatic ring stacking interactions which helps stabilizing the hairpin loop structure of the peptide. | Besides, there exists H-bond and aromatic ring stacking interactions which helps stabilizing the hairpin loop structure of the peptide. | ||
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| - | Along with | + | Along with TP-1, there exists three linear derivatives: <scene name='67/671725/1ma4/3'>TPY4</scene>, TPF4 and TPA4 as shown below. |
[[Image:derivatives.jpg]] | [[Image:derivatives.jpg]] | ||
| - | Of those 3 linear derivatives of | + | Of those 3 linear derivatives of TP-1, TPA4 was inactive which was due to its incapability to form hairpin loop structure. This guided to the conclusion that linear Tachyplesin analogues do not show preferential affinity for LPS. Therefore, the hairpin properties of the peptide seems to be important for recognition of lipopolysaccharides and its biological activities. |
| - | + | TP-1 undergoes confirmation change in <scene name='67/671725/Tp_i_in_the_presence_of_lps/1'>presence of LPS </scene>. The backbone of the polypeptide becomes <scene name='67/671725/Conformation_change/5'>more rigid and twisted in presence of LPS, than in the presence of water </scene>, making it more stable. | |
== Mode of action == | == Mode of action == | ||
| - | + | TP-1 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 TP-1 with phosphate group and sachharides of LPS. Furthermore, interaction between hydrophobic residues of TPI with acyl chains of LPS strengthens the TP-1/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 TP-1 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 relevance == | == Importance and relevance == | ||
Revision as of 12:15, 30 December 2014
Introduction
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References
- ↑ 1.0 1.1 1.2 Laederach A, Andreotti AH, Fulton DB. Solution and micelle-bound structures of tachyplesin I and its active aromatic linear derivatives. Biochemistry. 2002 Oct 15;41(41):12359-68. PMID:12369825
- ↑ 2.0 2.1 Chen, Yixin, et al. "RGD-Tachyplesin inhibits tumor growth." Cancer research 61.6 (2001): 2434-2438.
- ↑ Kushibiki T, Kamiya M, Aizawa T, Kumaki Y, Kikukawa T, Mizuguchi M, Demura M, Kawabata SI, Kawano K. Interaction between tachyplesin I, an antimicrobial peptide derived from horseshoe crab, and lipopolysaccharide. Biochim Biophys Acta. 2014 Jan 2;1844(3):527-534. doi:, 10.1016/j.bbapap.2013.12.017. PMID:24389234 doi:http://dx.doi.org/10.1016/j.bbapap.2013.12.017
- ↑ Nakamura, Takanori, et al. "Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure." Journal of Biological Chemistry 263.32 (1988): 16709-16713
- ↑ Saravanan R, Mohanram H, Joshi M, Domadia PN, Torres J, Ruedl C, Bhattacharjya S. Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle: Mechanistic insights into outer-membrane permeabilization and endotoxin neutralization. Biochim Biophys Acta. 2012 Mar 23;1818(7):1613-1624. PMID:22464970 doi:10.1016/j.bbamem.2012.03.015
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