Kalicludine

Last updated

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.

Contents

Etymology

“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

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

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

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

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]

Related Research Articles

<span class="mw-page-title-main">Dendrotoxin</span> Chemical compound

Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes (Dendroaspis) that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions. Because of their high potency and selectivity for potassium channels, dendrotoxins have proven to be extremely useful as pharmacological tools for studying the structure and function of these ion channel proteins.

<span class="mw-page-title-main">Margatoxin</span>

Margatoxin (MgTX) is a peptide that selectively inhibits Kv1.3 voltage-dependent potassium channels. It is found in the venom of Centruroides margaritatus, also known as the Central American Bark Scorpion. Margatoxin was first discovered in 1993. It was purified from scorpion venom and its amino acid sequence was determined.

<span class="mw-page-title-main">Sea anemone neurotoxin</span>

Sea anemone neurotoxin is the name given to neurotoxins produced by sea anemones with related structure and function. Sea anemone neurotoxins can be divided in two functional groups that either specifically target the sodium channel or the potassium channel.

<span class="mw-page-title-main">Stichodactyla toxin</span> Protein family

Stichodactyla toxin is a 35-residue basic peptide from the sea anemone Stichodactyla helianthus that blocks a number of potassium channels. Related peptides form a conserved family of protein domains known as the ShkT domain. Another well-studied toxin of the family is BgK from Bunodosoma granulifera.

Halcurin is a polypeptide neurotoxin from the sea anemone Halcurias sp. Based on sequence homology to type 1 and type 2 sea anemone toxins it is thought to delay channel inactivation by binding to the extracellular site 3 on the voltage gated sodium channels in a membrane potential-dependent manner.

<span class="mw-page-title-main">Pandinus imperator (Pi3) toxin</span>

Pi3 toxin is a purified peptide derivative of the Pandinus imperator scorpion venom. It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, Pi2.

Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.

BgK is a neurotoxin found within secretions of the sea anemone Bunodosomagranulifera which blocks voltage-gated potassium channels, thus inhibiting neuronal repolarization.

Kaliseptine (AsKS) is a neurotoxin which can be found in the snakelocks anemone Anemonia viridis. It belongs to a class of sea anemone neurotoxins that inhibits voltage-gated potassium channels.

Blood-depressing substance-1 (BDS-1), also known as kappa-actitoxin-Avd4a, is a polypeptide found in the venom of the snakelocks anemone Anemonia sulcata. BDS-1 is a neurotoxin that modulates voltage-dependent potassium channels, in particular Kv3-family channels, as well as certain sodium channels. This polypeptide belongs to the sea anemone type 3 toxin peptide family.

HsTx1 is a toxin from the venom of the scorpion Heterometrus spinifer. HsTx1 is a very potent inhibitor of the rat Kv1.3 voltage-gated potassium channel.

Spinoxin is a 34-residue peptide neurotoxin isolated from the venom of the Malaysian black scorpion Heterometrus spinifer. It is part of the α-KTx6 subfamily and exerts its effects by inhibiting voltage-gated potassium channels, specifically Kv1.2 and Kv1.3.

SHTX is a toxin derived from the sea anemone Stichodactyla haddoni; there are four different subtypes, SHTX I, II, III and IV. SHTX I, II and III can paralyze crabs by acting on potassium channels, while SHTX IV works on sodium channels, and is lethal to crabs.

<span class="mw-page-title-main">ImKTx88</span>

ImKTx88 is a selective inhibitor of the Kv1 ion channel family that can be isolated from the venom of the Isometrus maculatus. This peptide belongs to the α-KTx subfamily and is classified as a pore-blocking toxin.

<span class="mw-page-title-main">BscTx3</span>

BcsTx3, also known as Kappa-actitoxin-Bsc4a, is a neurotoxin that blocks voltage-gated potassium channel (Kv1/KCNA). It is purified from the venom of Bunodosoma caissarum.

AsKC11 is a toxin found in the venom of the sea anemone, Anemonia sulcata. This toxin is part of the Kunitz peptide family and has been shown to be an activator of G protein-coupled inwardly-rectifying potassium (GIRK) channels 1/2, involved in the regulation of cellular excitability. 

Toxin BF9 is a Kunitz-type peptide, coming from snakes, with a dual functionality. The toxin is able to inhibit both serine proteases and potassium channels.

<span class="mw-page-title-main">LmKTT-1a</span> Scorpion Toxin

LmKTT-1a is a bifunctional Kunitz-type toxin belonging to the ẟ-KTx subfamily, which can be found in the venom of Lychasmucronatus. As a bifunctional toxin, it both inhibits trypsin activity and blocks Kv1 channels with a weak selectivity towards Kv1.3 channels.

Kunitz-type serine protease inhibitor APEKTx1 is a peptide toxin derived from the sea anemone Anthopleura elegantissima. This toxin has a dual function, acting both as a serine protease inhibitor and as a selective and potent pore blocker of Kv1.1, a shaker related voltage-gated potassium channel.

κ-KTx2.5 is a toxin found in the venom of the scorpion, Opisthacanthuscayaporum. The toxin belongs to the κ-KTx family, a channel blocker family that targets voltage-gated potassium channels (Kv) 1.1 and 1.4.

References

  1. ↑ "Q9TWG0: Summary Page on Protein Model Portal – PSI SBKB". proteinmodelportal.org. Retrieved 2016-10-11.
  2. ↑ 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.
  3. 1 2 3 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 .
  4. ↑ 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.
  5. 1 2 Castañeda, Olga; Harvey, Alan L. (2009). "Discovery and characterization of cnidarian peptide toxins that affect neuronal potassium ion channels". Toxicon. 54 (8): 1119–1124. doi:10.1016/j.toxicon.2009.02.032. PMID   19269305.
  6. ↑ 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. doi:10.1016/j.toxicon.2012.05.020. PMID   22683676.
  7. ↑ Honma, Tomohiro; Shiomi, Kazuo (2006). "Peptide Toxins in Sea Anemones: Structural and Functional Aspects". Marine Biotechnology. 8 (1): 1–10. doi:10.1007/s10126-005-5093-2. PMC   4271777 . PMID   16372161.
  8. 1 2 "KappaPI-actitoxin-Avd3b – Anemonia sulcata (Mediterranean snakelocks sea anemone)". uniprot.org. Retrieved 2016-10-11.{{cite journal}}: Cite journal requires |journal= (help)
  9. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.