17704452 (Howra Al-Badri), "Conotoxins"
Email this Mix
Slide 1 - Advanced Physiology300851“Independent investigation topic”Ion channels “Conotoxins”Howra al-badri (17704452)
Slide 2 - Overview
- What conotoxins are?
- Types of conotoxins
- What ion channels are involved?
- How alpha-conotoxins work on ion channels
- Classes of alpha-conotoxins “ImI”
- The use of conotoxins
Slide 3 - Conotoxins?
- What are they?
- cone snail venom genus Conus
- group of neurotoxic peptides
- Contain 10 to 30 amino acid residues
- One or more desulfide bonds
- (Lebbe et al. 2014).
Slide 4 - types of conotoxins?
- have 2 types of cysteine arrangements
- Competitive nicotinic acetylcholine receptor antagonist
- delays the inactivation of sodium channel
- potassium channel blocker
- calcium channel blocker
- Muscle-specific voltage-gated sodium channels
- Useful for investigating voltage-dependent sodium channels of excitable tissues
- (Gowd et al. 2008).
Slide 5 - Ion channel involved?
- Alpha-conotoxins act on different types of neuronal nicotinic acetylcholine receptors
- the most diverse and largest group of conotoxins family
- interact at the competitive site of the nicotinic acetylcholine receptors (nAChRs)
- acetylcholine-binding protein (AChBP)
- Polypeptides of a-conotoxins highly selective for blocking nAChRs and ligand-gated ion channels
- A7 is a neuronal nicotinic acetylcholine receptor
- has created much concern in medical field
- distributed across cerebral cortex and hippocampus
- (Luo et al. 2013), (Hopping et al. 2014).
- Their binding sites at the interfaces among the α7 receptors in a homopentameric channel
Slide 6 - Ion channel involved
- Loops A, B and C areas of the primary sequence, contain the positive residues of the binding site of the α-face
- In the acetylcholine-binding proteins, the stabilizations are established by the adjacent disulfide bonds in loop C
- loop C a-conotoxins disulfide bonds interact with
- (Lebbe et al, 2014)
- (Luo et al. 2013).
Slide 7 - ImI conotoxin
- Class of apha-conotoxins
- Has the greatest and complete structure-activity relationship concerning a7 nAChRs
- It delineates a separate binding site above the loop C
- Has an essential role for the contribution of:
- Hydrophobic connections among several alpha conotoxins hydrophobic residues
- Conserved proline
- AChBPs’ residues in the aromatic cage
- The amino acid residues needed for the interaction between ImI alpha conotoxins and nAChRs:
- Aspartatic acid, tryptophan and arginine
- (Lebbe et al, 2014)
- (Yu, Craik and Kaas, 2011)
Slide 8 - The use of alpha Conotoxins
- Alpha-conotoxins used for therapeutic purpose & science investigations
- Alpha-conotoxins used to design drugs to improve pain & cognition
- Target many neurological disorders:
- Parkinson’s disease
- Alzheimer’s disease
- attention deficit disorders
- Conotoxin drug Prialt®, treat intractable pain
- Ziconitide Conus magus omega-conotoxins used for analgesia
- Analogs of alpha-conotoxins MII nicotinic blocker conotoxin
- effective in the treatment of Parkinson’s disease.
- (Lebbe et al, 2014), (Fedosov et al. 2013), (Napier et al. 2012).
Slide 9 - The use of Conotoxins
- Can be used for science investigation
- Used as tools of research to determine how specific ion channels and receptors work
- omega-conotoxins important in neuroscience studies
- examine the sub-types of calcium channels
- other conotoxins are used to study schizophrenia
- (Livett, Gayler and Khalil, 2004), (Zaki et al. 2011).
Slide 10 - Summary
- What ion channel do alpha-conotoxins modulate?
- Nicotinic acetylcholine receptors
- Interact at the competitive site of the nAChRs
- Block ligand-gated ion channels and nAChRs
- What are they used for?
- Used to treat many neurological disorders
- Used for science investigations
- There different types of conotoxins each one of them:
- Modulate different ion channels
- Used for different purposes
Slide 11 - References
- Fedosov, A, Moshkovskiĭ, S, Kuznetsova, K, & Olivera, B 2013, '[Conotoxins: from the biodiversity of gastropods to new drugs]', Biomedit͡sinskai͡a Khimii͡a, 59, 3, pp. 267-294, MEDLINE, EBSCOhost, viewed 14 May 2015.
- Gowd, KH, Dewan, KK, Iengar, P, Krishnan, KS, & Balaram, P 2008, 'Probing peptide libraries from Conus achatinus using mass spectrometry and cDNA sequencing: identification of delta and omega-conotoxins', Journal of Mass Spectrometry: JMS, vol. 43, no. 6, pp. 791-805, viewed 10 May 2015, DOI 10.1002/jms.1377
- Hopping, G, Wang, CA, Hogg, RC, Nevin, ST, Lewis, RJ, Adams, DJ, & Alewood, PF 2014, 'Hydrophobic residues at position 10 of α-conotoxin PnIA influence subtype selectivity between α7 and α3β2 neuronal nicotinic acetylcholine receptors', Biochemical Pharmacology, vol. 91, no. 4, pp. 534-542, viewed 9 May 2015, DOI 10.1016/j.bcp.2014.07.025.
- Lebbe, EM, Peigneur, S, Wijesekara, I, & Tytgat, J 2014, 'Conotoxins targeting nicotinic acetylcholine receptors: an overview', Marine Drugs, vol. 12, no. 5, pp. 2970-3004.
- Livett, B, Gayler, K, & Khalil, Z 2004, 'Drugs from the sea: conopeptides as potential therapeutics', Current Medicinal Chemistry, 11, 13, pp. 1715-1723, viewed 14 May 2015, MEDLINE, EBSCOhost.
- Luo, S, Zhangsun, D, Wu, Y, Zhu, X, Hu, Y, McIntyre, M, et al. 2013, 'Characterization of a novel α-conotoxin from conus textile that selectively targets α6/α3β2β3 nicotinic acetylcholine receptors', The Journal Of Biological Chemistry, vol. 288, no. 2, pp. 894-902, viewed 10 May 2015, MEDLINE, EBSCOhost, DOI 10.1074/jbc.M112.427898
Slide 12 - Reference
- Napier, I, Klimis, H, Rycroft, B, Jin, A, Alewood, P, Motin, L, Adams, D, & Christie, M 2012, 'Intrathecal α-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain', Neuropharmacology, 62, 7, pp. 2202-2207, viewed 13 May 2015, DOI 10.1016/j.neuropharm.2012.01.016
- Yu, R, Craik, DJ, & Kaas, Q 2011, 'Blockade of neuronal α7-nAChR by α-conotoxin ImI explained by computational scanning and energy calculations', Plos Computational Biology, vol. 7, no. 3, p. e1002011. Available from: 10.1371/journal.pcbi.1002011.
- Zaki, N, Wolfsheimer, S, Nuel, G, & Khuri, S 2011, 'Conotoxin protein classification using free scores of words and support vector machines', BMC Bioinformatics, 12, p. 217, viewed 14 May 2015, MEDLINE, EBSCOhost, DOI 10.1186/1471-2105-12-217