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Mar Drugs
2022 Oct 31;2011:. doi: 10.3390/md20110686.
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Molecular and Functional Characterization of a Novel Kunitz-Type Toxin-like Peptide in the Giant Triton Snail Charonia tritonis.
Zhang G
,
Jia H
,
Luo L
,
Zhang Y
,
Cen X
,
Yao G
,
Zhang H
,
He M
,
Liu W
.
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It has been reported that the giant triton snail (Charonia tritonis) inserts its large proboscis and then injects venom or acid saliva from its salivary gland into its prey, the crown-of-thorns starfish Acanthaster planci (COTS), paralyzing it. A full-length cDNA sequence of the C. tritonis Ct-kunitzin gene was obtained by RACE PCR based on a transcriptomic database constructed by our laboratory (data not published), which contains an open reading frame (ORF) sequence with a length of 384 bp including a 1-32aa Kunitz domain. The Ct-kunitzin peptide was synthesized by solid-phase polypeptide methods according to its conserved amino acid sequence, with a molecular weight of 3746.0 as well as two disulfide bonds. Renatured Ct-kunitzin was injected into mice ventricles to evaluate its potential function. Compared with the normal control group (physiological saline), the spontaneous locomotor activity of the Ct-kunitzin group decreased significantly. There was a significant effect on Ct-kunitzin on mice grip strength in the grip strength test. In addition, Ct-kunitzin exhibited remarkable biological activity in suppressing pain in the pain thresholds test. There were no significant differences between the Ct-kunitzin group and the normal control group in terms of various hematological indexes and histopathological observations. When tested in COTS, the most significant histological change was the destruction, disorganization, and significant reduction in the amount of COTS tube feet tissues. Altogether, the potential paralyzing effect on mice suggests that Ct-kunitzin is a possible agent for novel drug development.
2022A1515010779 Natural Science Foundation of Guangdong Province, 42176129 National Natural Science Foundation of China, GML2019ZD0402 the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), 2020B1212060058 Planning Project of Guangdong Province, China. Guangdong Provincial Key Laboratory of Ap-plied Marine Biology
Figure 1. The full-length cDNA sequence of Ct-kunitzin and its deduced amino acid sequence. The KU domain is blue; the initiation codon site is the yellow upward-facing triangle; the termination codon site is the downward-facing triangle; the cysteine site is red.
Figure 2. Phylogenetic analysis of venom proteins containing Kunitz domains. (A). Multiple alignment of Ct-kunitzin with 15 different Kunitz peptides based on the conserved sequences. The alignment was generated with the ClustalX Multiple Sequence Alignment program (version 1.83). (B). The Neighbor-joining (NJ) tree was constructed based on amino acid sequences using MEGA software version 6.06. The numbers below the nodes show bootstrap support values from 1000 replicates.
Figure 3. Relative mRNA expression profiles of a selected toxin-like gene from the salivary gland tissues of C. tritonis. A p-value < 0.01 was considered highly significant (**).
Figure 4. Overview of the three-dimensional structure of Ct-kunitzin and homologous structural modeling of Ct-kunitzin and a template protein named conkunitzin-10 (DAC80558.1). (A) 3D models of Ct-kunitzin. The main secondary structure elements are colored, with the α helix in red and loops colored in green. (B) Homologous modeling based on a highly homologous protein. The structures are shown in cartoon form; light grey for Ct-kunitzin, red and green for conkunitzin-10 (DAC80558.1).
Figure 5. (A) HPLC and (B) mass spectra (ESI-MS) for Ct-kunitzin peptides.
Figure 6. Behavioral changes after Ct-kunitzin injection in mice. (A). Effects of Ct-kunitzin on spontaneous locomotor activity in mice (mean ± SD, n = 6). (B). Grip strength. (C). Rota-rod test. (D). Mechanical PWT. Statistical significance values are indicated as *: p < 0.05, **: p < 0.01.
Figure 7. Mice plasma biochemistry on the 7th day after injection of Ct-kunitzin (mean ± SD, n = 6). (A). Serum levels of CRE. (B). Serum levels of BUN. (C). Serum levels of UA. (D). Serum levels of ALT.
Figure 8. (A–F). Pathological observation of tissues in mice (H&E staining, ×200). (A,C,E) Control group with Sham injection. (B,D,F). Experimental group injected with Ct-kunitzin.
Figure 9. Pathological changes of tube feet tissue of COTS within 1 h of Ct-kunitzin injection. Representative histopathological pictures of the sham control stained by Masson’s Trichrome procedure. (A) Control group injected with saline. (B) Experimental group injected with Ct-kunitzin.
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