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Family: Cys_Knot_tox (PF17486)

Summary: Cystine knot toxins

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This is the Wikipedia entry entitled "Inhibitor cystine knot". More...

Inhibitor cystine knot Edit Wikipedia article

Topology of an inhibitor cystine knot. This example shows three beta strands with disulphides shown in yellow. Not all examples contain the central (purple) strand.
MCh-1: A plant inhibitor cystine knot peptide from Momordica charantia. PDB entry 2m2q.[1]

An inhibitor cystine knot (aka ICK or Knottin) is a protein structural motif containing three disulfide bridges. Along with the sections of polypeptide between them, two disulfides form a loop through which the third disulfide bond (linking the 3rd and 6th cysteine in the sequence) passes, forming a knot. The motif is common in invertebrate toxins such as those from arachnids and molluscs. The motif is also found in some inhibitor proteins found in plants, but the plant and animal motifs are thought to be a product of convergent evolution.[2] The ICK motif is a very stable protein structure which is resistant to heat denaturation and proteolysis.[3] ICK peptide components of venoms target voltage-gated ion channels but members of the family also act as antibacterial and haemolytic agents.[4] Plant ICK proteins are often protease inhibitors. Because of their stability, ICK motifs are being developed as possible therapeutics.[5]

The mammalian proteins Agouti signalling peptide and Agouti related peptide are the only know mammalian examples of this motif. Both are neuropeptides involved in cell signalling. The former is responsible for hair (fur) colouration.

The motif is similar to the cyclic cystine knot or cyclotide, but lacks the cyclisation of the polypeptide backbone which is present in the latter family. The growth factor cystine knot (GFCK) shares the motif but its topology is such that it is the bond between the first and fourth disulphide which threads through the loop.

Proteins which contain the ICK motif

References

  1. ^ He, W. J.; Chan, L. Y.; Clark, R. J.; Tang, J.; Zeng, G. Z.; Franco, O. L.; Cantacessi, C.; Craik, D. J.; Daly, N. L.; Tan, N. H. (2013). Driscoll, Paul C, ed. "Novel Inhibitor Cystine Knot Peptides from Momordica charantia". PLoS ONE. 8 (10): e75334. doi:10.1371/journal.pone.0075334. PMC 3792974Freely accessible. PMID 24116036. 
  2. ^ Zhu, S.; Darbon, H.; Dyason, K.; Verdonck, F.; Tytgat, J. (2003). "Evolutionary origin of inhibitor cystine knot peptides". The FASEB Journal. 17 (12): 1765–1767. doi:10.1096/fj.02-1044fje. PMID 12958203. 
  3. ^ Daly, N. L.; Craik, D. J. (2011). "Bioactive cystine knot proteins". Current Opinion in Chemical Biology. 15 (3): 362–368. doi:10.1016/j.cbpa.2011.02.008. PMID 21362584. 
  4. ^ Craik, D. J.; Daly, N. L.; Waine, C. (2001). "The cystine knot motif in toxins and implications for drug design". Toxicon. 39 (1): 43–60. doi:10.1016/S0041-0101(00)00160-4. PMID 10936622. 
  5. ^ Baeriswyl, V.; Heinis, C. (2013). "Polycyclic Peptide Therapeutics". ChemMedChem. 8 (3): 377–384. doi:10.1002/cmdc.201200513. PMID 23355488. 

External links


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Cystine knot toxins Provide feedback

This family is found in Araneaea (spiders) and family members are venomus peptides with 4 disulfide bonds. Cystine knot toxins (CKTs) are small, compact molecules cross-linked by three to five disulfide bonds and are often the key contributors to the activity and potency of the venom [1]. While these disulfide-rich peptides can adopt a number of different structural motifs, three of the most observed structural scaffold motifs are the inhibitor cystine knot (ICK) and the disulfide-directed beta-hairpin (DDH) and Kunitz motif. These venomus peptides mainly act on membrane proteins in electro-excitable cell membranes by modulating voltage-activated sodium (NaV), calcium (CaV), and potassium (KV) channels, acid-sensing ion channels (ASICs), transient receptor potential (TRP) channels, and mechanosensitive channels (MSCs) [2].

Literature references

  1. Chen J, Deng M, He Q, Meng E, Jiang L, Liao Z, Rong M, Liang S;, Cell Mol Life Sci. 2008;65:2431-2444.: Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao. PUBMED:18581053 EPMC:18581053

  2. Windley MJ, Herzig V, Dziemborowicz SA, Hardy MC, King GF, Nicholson GM;, Toxins (Basel). 2012;4:191-227.: Spider-venom peptides as bioinsecticides. PUBMED:22741062 EPMC:22741062


This tab holds annotation information from the InterPro database.

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Domain organisation

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Pfam Clan

This family is a member of clan Cystine-knot (CL0079), which has the following description:

The cytokine families in this clan have the cystine-knot fold. In this 6 cysteines form three disulphide bridges that are interlinked.

The clan contains the following 14 members:

Coagulin Cys_knot Cys_Knot_tox D_CNTX DAN Hormone_6 IL17 m_DGTX_Dc1a_b_c NGF Noggin PDGF Sclerostin Spaetzle TGF_beta

Alignments

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(9)
Full
(0)
Representative proteomes UniProt
(18)
NCBI
(19)
Meta
(0)
RP15
(0)
RP35
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RP55
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RP75
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Curation and family details

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Curation View help on the curation process

This family is new in this Pfam release.

Seed source: PRODOM:PD015053
Previous IDs: none
Type: Family
Author: El-Gebali S
Number in seed: 9
Number in full: 0
Average length of the domain: 0.00 aa
Average identity of full alignment: 0 %
Average coverage of the sequence by the domain: 0.00 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 53.3 68.8
Noise cut-off 24.1 20.0
Model length: 70
Family (HMM) version: 1
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