TxIB (P05345) Protein Card

General Information
Name TxIB
Organism Conus textile (Cloth-of-gold cone)
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Protein precursor TxIB precursor (5225)
Notes
  • You et al.(2019) injected TxIB in mice and reported the behaviour of the animal: TxIB inhibited the NIC-induced conditioned place preference expression and reinstatement with a dose-dependent manner. It had no significant effect on locomotor activity after intracerebroventricular injection in mice.
  • Mao et al.(2022) show that TxIB injection improved behavioural abnormality caused by alcohol withdrawal in the zebrafish model. The TxIB injection also altered gene expression mainly in the calcium signalling pathway. The results suggest the potential of TxIB in alcohol withdrawal treatment.
    		•

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

    Sequence
    GCCSDPPCRNKHPDLC(nh2)
    Modified residues
    positionsymbolname
    17nh2C-term amidation
    Sequence evidence nucleic acid level
    Average Mass 1739.97
    Monoisotopic Mass 1738.68
    Isoelectric Point 8.31
    Extinction Coefficient [280nm] -1.00

    Activity

    IC50: Nicotinic acetylcholine receptors

    TargetOrganismIC50AgonistRef
    α1β1δεM. musculus>10uM10uM AChLuo,S. et al. (2013)
    α2β2R. norvegicus>10uM100uM AChLuo,S. et al. (2013)
    α2β4R. norvegicus>10uM100uM AChLuo,S. et al. (2013)
    α3β2R. norvegicus>10uM100uM AChLuo,S. et al. (2013)
    α3β4R. norvegicus >10uM100uM AChLuo,S. et al. (2013)
    α4β2R. norvegicus >10uM100uM AChLuo,S. et al. (2013)
    α4β4R. norvegicus >10uM100uM AChLuo,S. et al. (2013)
    α6/α3β2β3H. sapiens291 nM[255-332]100uM AChHone et al. (2018)
    R. norvegicus41.7nM[32.1-54.22]100uM AChYu,J. et al. (2018)
    28.4nM+/-15100uM AChLuo,S. et al. (2013)
    207 nM[175-244]100uM AChHone et al. (2018)
    α6/α3β4H. sapiens402 nM[338-477] 300uM AchHone et al. (2018)
    R. norvegicus>10uM100uM AChLuo,S. et al. (2013)
    >10 uM300uM AchHone et al. (2018)
    α7R. norvegicus>10uM200uM AChLuo,S. et al. (2013)
    α9α10R. norvegicus>10uM10uM AChLuo,S. et al. (2013)

    Percentage inhibition: Nicotinic acetylcholine receptors

    TargetOrganism% inhibitionConcentrationAgonistRef
    α6β2β3M. musculus42100 nMAch (100 uM)Li,X. et al. (2020)
    α6/α3β2β3R. norvegicus86.7+/-6.71 uMZhang,B. et al. (2021)

    Synthetic variants
    TxIB[C1Xch,C3Xch]G(Xch)CSDPP(Xch)RNKHPDLC(nh2)
    TxIB[C2Xch,C4Xch]GC(Xch)SDPPCRNKHPDL(Xch)(nh2)
    TxIB[K11A]GCCSDPPCRNAHPDLC(nh2)
    TxIB[insC_G]GCCSDPPCRNKHPDLCG
    TxIB[insC_M]GCCSDPPCRNKHPDLCM
    TxIB[insN_GAAG] cyclicGAAGGCCSDPPCRNKHPDLC
    TxIB[insN_GAGAGAAG] cyclicGAGAAGGCCSDPPCRNKHPDLC
    TxIB[insN_GGAAGAG] cyclicGGAAGAGGCCSDPPCRNKHPDLC
    TxIB[insN_GGAAG] cyclicGGAAGGCCSDPPCRNKHPDLC

    References
    Luo,S., Zhangsun,D., Wu,Y., Zhu,X., Hu,Y., McIntyre,M., Christensen,S., Akcan,M., Craik,D.J. and McIntosh,J.M. (2013) Characterization of a novel α-conotoxin from conus textile that selectively targets α6/α3β2β3 nicotinic acetylcholine receptors. J. Biol. Chem. 288:894-902
    Hone, A.J., Talley, T.T., Bobango, J., Melo, C.H., Hararah, F., Gajewiak, J., Christensen, S., Harvey, P.J., Craik, D.J. and McIntosh, J.M. (2018) Molecular determinants of α-conotoxin potency for inhibition of human and rat α6β4 nicotinic acetylcholine receptors Journal of Biological Chemistry 293:17838-17852
    Li,X., Wang,S., Zhu,X., Zhangsun,D., Wu,Y. and Luo,S (2020) Effects of Cyclization on Activity and Stability of α-Conotoxin TxIB Mar Drugs 18
    You,S., Li,X., Xiong,J., Zhu,X., Zhangsun,D., Zhu,X. and Luo,S. (2019) α-Conotoxin TxIB: A Uniquely Selective Ligand for α6/α3β2β3 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Conditioned Place Preference in Mice Mar Drugs 17:490
    Yu,J., Zhu,X., Yang,Y., Luo,S. and Zhangsun,D. (2018) Expression in Escherichia coli of fusion protein comprising α-conotoxin TxIB and preservation of selectivity to nicotinic acetylcholine receptors in the purified product Chem Biol Drug Des 91:349-358
    Zhang,B., Ren,M., Xiong,Y., Li,H., Wu,Y., Fu,Y., Zhangsun,D., Dong,S. and Luo,S. (2021) Cysteine [2,4] Disulfide Bond as a New Modifiable Site of α-Conotoxin TxIB. Mar Drugs 19
    Mao,K., Li,X., Chen,Z., Dong,X., Zhangsun,D., Zhu,X., and Luo,S. (2022) α-Conotoxin TxIB Improved Behavioral Abnormality and Changed Gene Expression in Zebrafish (Danio rerio) Induced by Alcohol Withdrawal Frontiers in pharmacology 13:802917

    Internal links
    Protein Precursor TxIB precursor (5225)
    Nucleic acids
    Structure Solution structure of a Novel Alpha-Conotoxin TxIB

    External links

    Tools