Tachyplesin: Difference between revisions
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The sequence adapts an antiparallel β-sheet (hairpin) conformation in solution, with a <scene name='67/671725/Beta_turn_tp-1/2'>β-turn</scene> for the centrally located residues <scene name='67/671725/Tyrargglyile/3'>Tyr-Arg-Gly-Ile</scene>, stabilized by two cross-strand <scene name='67/671725/Disulfide_bonds/4'> disulfide bonds </scene> between Cys³-Cys¹⁶ and Cys⁷-Cys¹²<ref name=Saravanan>PMID:22464970</ref><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>, and [http://en.wikipedia.org/wiki/Protein_primary_structure C-terminus amidation]. In addition there are H-bonds and aromatic rings stacking interactions which helps stabilize the hairpin loop structure of the peptide. | The sequence adapts an antiparallel β-sheet (hairpin) conformation in solution, with a <scene name='67/671725/Beta_turn_tp-1/2'>β-turn</scene> for the centrally located residues <scene name='67/671725/Tyrargglyile/3'>Tyr-Arg-Gly-Ile</scene>, stabilized by two cross-strand <scene name='67/671725/Disulfide_bonds/4'> disulfide bonds </scene> between Cys³-Cys¹⁶ and Cys⁷-Cys¹²<ref name=Saravanan>PMID:22464970</ref><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>, and [http://en.wikipedia.org/wiki/Protein_primary_structure C-terminus amidation]. In addition there are H-bonds and aromatic rings stacking interactions which helps stabilize the hairpin loop structure of the peptide. | ||
[http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] studies have shown that TP-I undergoes a conformational change in <scene name='67/671725/Tp_i_in_the_presence_of_lps/1'>presence of LPS, </scene><scene name='67/671725/Conformation_change/8'>making it more rigid and twisted than in the presence of water</scene><ref name=Kushibiki>PMID:24389234</ref>. Moreover docking model suggests the stabilized structure of TP-I in presence of LPS, which is gained by binding between N and C termini of TP-I to LPS. The conformational change of TP-I seems to be crucial for its antimicrobial activity, since rearrangement of TP-I structure makes it more amphiphilic to negatively charged membrane of bacteria and fungus | [http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance NMR] studies have shown that TP-I undergoes a conformational change in <scene name='67/671725/Tp_i_in_the_presence_of_lps/1'>presence of LPS, </scene><scene name='67/671725/Conformation_change/8'>making it more rigid and twisted than in the presence of water</scene><ref name=Kushibiki>PMID:24389234</ref>. Moreover docking model suggests the stabilized structure of TP-I in presence of LPS, which is gained by binding between N and C termini of TP-I to LPS. The conformational change of TP-I seems to be crucial for its antimicrobial activity, since rearrangement of TP-I structure makes it more amphiphilic to negatively charged membrane of bacteria and fungus<ref name=Laederach>PMID:12369825</ref>. | ||
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The β-hairpin topology of CDT is sustained by the <scene name='67/671725/Cdthaipin/2'>unique packing interactions</scene> between the aromatic ring of Trp2 and the side-chain of nonpolar amino acid of Val5 and the cationic side-chain of residue Arg11. | The β-hairpin topology of CDT is sustained by the <scene name='67/671725/Cdthaipin/2'>unique packing interactions</scene> between the aromatic ring of Trp2 and the side-chain of nonpolar amino acid of Val5 and the cationic side-chain of residue Arg11. | ||
There is a close proximity between residues <scene name='67/671725/Cdtnoe/1'>Trp2 and Ile9</scene>, supported by the [http://en.wikipedia.org/wiki/Nuclear_Overhauser_effect nuclear overhauser effects (NOEs)] involving [http://en.wikipedia.org/wiki/Indole indole] ring protons of Trp2 with side-chain proton of Ile9. These packing interactions have rendered an approximate anti-parallel orientation of the hairpin structure of CDT in presence of LPS. | There is a close proximity between residues <scene name='67/671725/Cdtnoe/1'>Trp2 and Ile9</scene>, supported by the [http://en.wikipedia.org/wiki/Nuclear_Overhauser_effect nuclear overhauser effects (NOEs)] involving [http://en.wikipedia.org/wiki/Indole indole] ring protons of Trp2 with side-chain proton of Ile9. These packing interactions have rendered an approximate anti-parallel orientation of the hairpin structure of CDT in presence of LPS. | ||
The β-hairpin like structure of CDT displays an extended <font color='darkblue'>positively charged</font> surface patch of <scene name='67/671725/Cdtr4r7r12r13/1'>residues Arg 4, 7, 12 and 13</scene>. These positively charged basic residues interacts with the anionic phosphate groups of LPS | The β-hairpin like structure of CDT displays an extended <font color='darkblue'>positively charged</font> surface patch of <scene name='67/671725/Cdtr4r7r12r13/1'>residues Arg 4, 7, 12 and 13</scene>. These positively charged basic residues interacts with the anionic phosphate groups of LPS, that leads to a plausible disruption or fluidization of LPS structures. This facilitates traversal of the peptide through the LPS-outer membrane<ref name=Saravanan>PMID:22464970</ref>. | ||
== Mode of action == | == Mode of action == | ||
