TxIA (P02881) Protein Card

General Information
Name TxIA (named by ConoServer)
Alternative name(s) Tx1.1,Tx1a
Organism Conus textile (Cloth-of-gold cone)
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Protein precursor TxIA precursor (2882)
Notes Dobson et al.,2012 reported that hydroxyproline on 6 and 7 of TxIA can be detected, but the un-modified TxIA is the most abundant.

Classification
Conopeptide class conotoxin
Gene superfamily A superfamily
Cysteine framework I
Pharmacological family alpha conotoxin

Sequence
GCCSRPPCIANNPDLC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Sequence evidence protein level
Average Mass 1657.91
Monoisotopic Mass 1656.66
Isoelectric Point 7.00
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α3β2R. norvegicus(mutant α3(I186R)β2)60.4 nM[50.9-71.6]-1.033ACh (100 μM)Beissner,M. et al. (2012)
3.6nM[2.9-4.4]AchDutertre,S. et al. (2007)
2 nM[1.68-2.43]-1.062ACh (100 μM)Beissner,M. et al. (2012)
4.6 nM[3.6-5.8]ACh (100 uM)El Hamdaoui,Y. et al. (2019)
5.4 nMACh (100 uM)Wu,Y. et al. (2014)
α4β2R. norvegicus(mutant α4(R185I)β2)18.1 nM[15.2-21.6]-0.813ACh (100 μM)Beissner,M. et al. (2012)
α7R. norvegicus1812 nM[1555-2111]nicotine(100 uM)El Hamdaoui,Y. et al. (2019)
392nM[310-490]nicotineDutertre,S. et al. (2007)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
AChBPL. stagnalis1.7nM+/-0.7I-Bgt(10 uM)Dutertre,S. et al. (2007)

Synthetic variants
TxIA[A10L]GCCSRPPCILNNPDLC(nh2)
TxIA[R5D, ribbon] deamidatedGCCSDPPCIANNPDLC
TxIA[R5N,ribbon] deamidatedGCCSNPPCIANNPDLC
TxIA[beads]GCCSRPPCIANNPDLC(nh2)
TxIA[ribbon]GCCSRPPCIANNPDLC(nh2)
TxIA[ribbon] deamidatedGCCSRPPCIANNPDLC

References
Dutertre,S., Ulens,C., Büttner,R., Fish,A., van Elk,R., Kendel,Y., Hopping,G., Alewood,P.F., Schroeder,C., Nicke,A., Smit,A.B., Sixma,T.K. and Lewis,R.J. (2007) AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J. 26:3858-3867
Dobson,R., Collodoro,M., Gilles,N., Turtoi,A., De Pauw,E. and Quinton,L. (2012) Secretion and maturation of conotoxins in the venom ducts of Conus textile. Toxicon 60:1370-1379
El Hamdaoui,Y., Wu,X., Clark,R.J., Giribaldi,J., Anangi,R., Craik,D.J., King,G.F., Dutertre,S., Kaas,Q., Herzig,V. and Nicke,A. (2019) Periplasmic Expression of 4/7 α-Conotoxin TxIA Analogs in E. coli Favors Ribbon Isomer Formation - Suggestion of a Binding Mode at the α7 nAChR. Front Pharmacol 10:577
Beissner,M., Dutertre,S., Schemm,R., Danker,T., Sporning,A., Grubmüller,H. and Nicke,A. (2012) Efficient binding of 4/7 α-conotoxins to nicotinic α4β2 receptors is prevented by Arg185 and Pro195 in the α4 subunit Mol. Pharmacol 82:711-718
Wu,Y., Wu,X., Yu,J., Zhu,X., Zhangsun,D. and Luo,S. (2014) Influence of disulfide connectivity on structure and bioactivity of α-conotoxin TxIA Molecules 19:966-979

Internal links
Protein Precursor TxIA precursor (2882)
Nucleic acids
Structure

External links

Tools