Conotoxins, the disulfide rich conopeptides, are classified according to three schemes: the similarities between the ER signal sequence of the conotoxin precursors (gene superfamilies), the cysteine patterns of conotoxin mature peptide regions (cysteine frameworks), and the specificities to pharmacological targets (pharmacological families). This page provides a brief introduction to the cysteine frameworks used in ConoServer. The two other classification schemes are detailed in separate pages accessible from the menu on the left. A more comprehensive discussion of the conopeptide classification schemes can be found in Kaas et al. Toxicon 2010 [1].
During the maturation process of proteins in eukaryote, cysteine residues are oxidised and form disulfide bridges, which are important to maintain protein shapes. Through this shape, disulfide bonds play en essential role for the stability and the activity of proteins. Cysteine frameworks are defined in ConoServer by the arrangement of cysteines along the primary sequence of the conopeptide mature region in the precursor protein. As described in Table 1, the cysteine frameworks are defined by the number of cysteines and the number of residues (none or at least one) between consecutive cysteines.
At an early stage of conopeptide discovery, the disulfide connectivities were also included in the definition. Because the cysteine frameworks are now only defined according to the primary sequence, they can be attributed without determining the disulfide connectivities [1]. Table 1 also gives the disulfide connectivies that have been presently identified for each cysteine frameworks. Additional connectivities may be discovered in the future for each cysteine framework.
Framework | Cystine pattern | # cysteines | Connectivity | Reference |
---|---|---|---|---|
I | CC-C-C | 4 | I-III, II-IV | Gray,W.R. et al. (1981) J. Biol. Chem. 256:4734-4740 |
II | CCC-C-C-C | 6 | Ramilo,C. et al. (1992) Biochemistry 31:9919-9926 | |
III | CC-C-C-CC | 6 | Sato,S. et al. (1983) FEBS Lett. 155:277-280 | |
IV | CC-C-C-C-C | 6 | I-V, II-III, IV-VI | Fainzilber,M. et al. (1995) Biochemistry 34:8649-8656 |
V | CC-CC | 4 | I-III, II-IV | Walker,C.S. et al. (1999) J. Biol. Chem. 274:30664-30671 |
VI/VII | C-C-CC-C-C | 6 | I-IV, II-V, III-VI | Olivera,B.M. et al. (1984) Biochemistry 23:5087-5090 |
VIII | C-C-C-C-C-C-C-C-C-C | 10 | England,L.J. et al. (1998) Science 281:575-578 | |
IX | C-C-C-C-C-C | 6 | I-IV, II-V, III-VI | Lirazan,M.B. et al. (2000) Biochemistry 39:1583-1588 |
X | CC-C.[PO]C | 4 | I-IV, II-III | Balaji,R.A. et al. (2000) J. Biol. Chem. 275:39516-39522 |
XI | C-C-CC-CC-C-C | 8 | I-IV, II-VI, III-VII, V-VIII | Jimenez,E.C. et al. (2003) J. Neurochem. 85:610-621 |
XII | C-C-C-C-CC-C-C | 8 | Brown,M.A. et al. (2005) Biochemistry 44:9150-9159 | |
XIII | C-C-C-CC-C-C-C | 8 | Aguilar,M.B. et al. (2005) Biochemistry 44:11130-11136 | |
XIV | C-C-C-C | 4 | I-III, II-IV | Moller,C. et al. (2005) Biochemistry 44:15986-15996 |
XV | C-C-CC-C-C-C-C | 8 | Peng,C. et al. (2008) Peptides 29:985-991 | |
XVI | C-C-CC | 4 | Pi,C. et al. (2006) Genomics 88:809-819 | |
XVII | C-C-CC-C-CC-C | 8 | Yuan,D.D. et al. (2008) Peptides 29:1521-1525 | |
XVIII | C-C-CC-CC | 6 | Chen,J.S. et al. (1999) J Nat Toxins 8:341-349 | |
XIX | C-C-C-CCC-C-C-C-C | 10 | Chen,P. et al. (2008) Toxicon 52:139-145 | |
XX | C-CC-C-CC-C-C-C-C | 10 | Loughnan,M.L. et al. (2009) Biochemistry 48:3717-3729 | |
XXI | CC-C-C-C-CC-C-C-C | 10 | Möller,C. and Marí,F. (2011) Biopolymers 96:158-165 | |
XXII | C-C-C-C-C-C-C-C | 8 | Elliger,C.A. et al. (2011) Toxicon 57:311-322 | |
XXIII | C-C-C-CC-C | 6 | Ye,M. et al. (2012) J Biol Chem 287:14973-14983 | |
XXIV | C-CC-C | 4 | Luo,S. et al. (2013) PLoS ONE 8 | |
XXV | C-C-C-C-CC | 6 | Aguilar,M.B. et al. (2013) Peptides 41:38-44 | |
XXVI | C-C-C-C-CC-CC | 8 | Bernáldez,J. et al. (2013) Mar Drugs 11:1188-1202 | |
XXVII | C-C-C-CCC-C-C | 8 | Jin,A.H. et al. (2015) Proc. Biol. Sci. 282 | |
XXVIII | C-C-C-CC-C-C-C-C-C | 10 | Lu et al. (2017) Peptides, 94, pp.64-70 94:64-70 | |
XXIX | CCC-C-CC-C-C | 8 | Bernáldez-Sarabia,J. et al. (2019) Toxins 11:128 | |
XXX | C-C-CCC-C-C-C-CC | 10 | Bernáldez-Sarabia,J. et al. (2019) Toxins 11:128 | |
XXXII | C-CC-C-C-C | 6 | Kancherla,A.K. et al. (2015) ACS Chem. Biol. 10:1847-1860 | |
XXXIII | C-C-C-C-C-C-C-C-C-C-C-C | 12 | Pardos-Blas,J.R. et al. (2019) Marine drugs 17:453 |
[1] | Kaas,Q. et al. (2010) Toxicon 55:1491-1509 |
ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.
The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).
Contacts:
David Craik
Quentin Kaas
Last updated: Monday 30 January 2023