Kalicludine
Kalicludine (AsKC) is a blocker of the voltage-dependent potassium channel Kv1.2 found in the snakeslocks anemone Anemonia viridis (Anemonia sulcata), which it uses to paralyse prey.
Etymology
[edit]"Kali", abbreviated from the Latin word "kalium", equals potassium. "Cludine" means to block or to enclose, as it is derived from the Latin verb "cludere".
Source, family and homology
[edit]Kalicludine (uniprot ID: Q9TWG0) is also known as KappaPI-actitoxin-Avd3b or as Kunitz-type serine protease inhibitor kalicludine-1.[1] Thus, kalicludines are part of the Kunitz-type inhibitor superfamily. The Kunitz-type scaffold is found both in inhibitors of proteolytic enzymes and in toxins.[2] Other members of this superfamily are the pancreatic trypsin inhibitors (BPTI), which are potent Kunitz-type protease inhibitors, and dendrotoxins. Kalicludine has 40% homology with BPTIs.[3] The most represented sequences of this group corresponds with kalicludine-3 and kalicludine-4, a recently found polypeptide.
A. sulcata kalicludines include AsKC1, AsKC2, and AsKC3.,[4] which are related to Bunodosoma granulifera toxin k (BgK) and Stichodactyla helianthus toxin k (ShK).[3] A different, less abundant, protein is AsKC1a, which has a supplementary residue at the C-terminus when compared with kalicludine-1. Furthermore, a level of amino acid sequence identity and similarity of ≥43% and ≥50% was found between both A. sulcata Kunitz-type protease inhibitors SA5 II, SA5 III and AsKC1 – AsKC15.
Kalicludine has 48% identity with the amyloid A4 homologue, which is implicated in Alzheimer's disease.[5]
Structure
[edit]The kalicludine isotoxins have similar molecular size and a similar biological function.[6] They contain three amino acid residues that are important for trypsin binding: Lys-15, Ala-16, and Ile-19 in BPTI. AsKCs have a replacement at position 19 (Ile → Pro), which results in less inhibitory action than BPTI.[7]
Mode of action
[edit]Kalicludine is stored in nematocysts or located in extracellular regions. It is known to be a dual-function toxin, able to inhibit both the serine protease trypsin (Kd=30 nM) and the voltage-gated potassium channels Kv1.2/KCNA2 (IC50=2800 nM).[8] Kalicludines and dendrotoxins compete for binding to these Kv channels.[9]
The kalicludine sequence is homologous to the sequence of dendrotoxins, in particular DTX 1 (dendrotoxin 1), potent blockers of Kv channels. Kalicludines have from 38 to 42% homologies with DTX.[3] Both kalicludines and dendrotoxins increase the release of acetylcholine and enhance the duration of action potentials (AP).[8]
Toxicity and symptoms
[edit]Kv channel blocking dendrotoxins, and thus possibly also kalicludines, often lead to overstimulation of the cholinergic system, and subsequently to neuromuscular block and cardiovascular depression.[5]
References
[edit]- ^ "Q9TWG0: Summary Page on Protein Model Portal – PSI SBKB". proteinmodelportal.org. Retrieved 2016-10-11.
- ^ Kozlov, Sergey; Grishin, Eugene (2011). "The mining of toxin-like polypeptides from EST database by single residue distribution analysis". BMC Genomics. 12: 88. doi:10.1186/1471-2164-12-88. PMC 3040730. PMID 21281459.
- ^ a b c Messerli, Shanta M.; Greenberg, Robert M. (2006). "Cnidarian Toxins Acting on Voltage-Gated Ion Channels". Marine Drugs. 4 (3): 70–81. doi:10.3390/md403070. PMC 3663410.
- ^ Schweitz, H.; Bruhn, T.; Guillemare, E.; Moinier, D.; Lancelin, J.-M.; Beress, L.; Lazdunski, M. (1995). "Kalicludines and Kaliseptine". Journal of Biological Chemistry. 270 (42): 25121–25126. doi:10.1074/jbc.270.42.25121. PMID 7559645.
- ^ a b Castañeda, Olga; Harvey, Alan L. (2009). "Discovery and characterization of cnidarian peptide toxins that affect neuronal potassium ion channels". Toxicon. 54 (8): 1119–1124. Bibcode:2009Txcn...54.1119C. doi:10.1016/j.toxicon.2009.02.032. PMID 19269305.
- ^ Oliveira, J. S.; Fuentes-Silva, D; King, G. F. (2012). "Development of a rational nomenclature for naming peptide and protein toxins from sea anemones". Toxicon. 60 (4): 539–550. Bibcode:2012Txcn...60..539O. doi:10.1016/j.toxicon.2012.05.020. PMID 22683676.
- ^ Honma, Tomohiro; Shiomi, Kazuo (2006). "Peptide Toxins in Sea Anemones: Structural and Functional Aspects". Marine Biotechnology. 8 (1): 1–10. Bibcode:2006MarBt...8....1H. doi:10.1007/s10126-005-5093-2. PMC 4271777. PMID 16372161.
- ^ a b "KappaPI-actitoxin-Avd3b – Anemonia sulcata (Mediterranean snakelocks sea anemone)". uniprot.org. Retrieved 2016-10-11.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Aneiros, Abel; García, Ileana; Martínez, Josér.; Harvey, Alan L.; Anderson, Amanda J.; Marshall, David L.; Engström, Åke; Hellman, Ulf; Karlsson, Evert (1993). "A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. isolation, amino acid sequence and biological activity". Biochimica et Biophysica Acta (BBA) - General Subjects. 1157 (1): 86–92. doi:10.1016/0304-4165(93)90082-J. PMID 8098956.