MI (P00023) Protein Card

General Information
Name MI
Alternative name(s) M1
Organism Conus magus (Magus cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Notes MI binds at the alpha/delta interface of the muscle type nAChR (Sine et al. 1995; Cortez et al. 2007). This toxin was used to study the specific opening patterns elicited by agonist binding at either the alpha-gamma, alpha-deta and alpha-epsilon interface (Stock et al. 2014; Dudel et al. 2014)

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

Sequence
GRCCHPACGKNYSC(nh2)
Modified residues
positionsymbolname
15nh2C-term amidation
Sequence evidence protein level
Average Mass 1493.71
Monoisotopic Mass 1492.56
Isoelectric Point 11.81
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50AgonistRef
α1β1δM. musculus400pM+/-1701-10uM AchJacobsen,R.B. et al. (1999)
α1β1γδM. musculus400pM+/-101-10uM AchJacobsen,R.B. et al. (1999)
12nM500nM AchJohnson,D.S. et al. (1995)
α1β1;γM. musculus18uM+/-51-10uM AchJacobsen,R.B. et al. (1999)
α2β2R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α2β4R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α3β2R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α3β4R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α4β2R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α4β4R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α7R. norvegicus>5uM500uM AchJohnson,D.S. et al. (1995)
α9R. norvegicus>5uM100uM AchJohnson,D.S. et al. (1995)

Kd: Nicotinic acetylcholine receptors

TargetOrganismKdRef
α1β1γδM. musculus1.4nM+/-0.1Jacobsen,R.B. et al. (1999)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
α1β1γδT. californica89.1nM+/-9.12nM [3H]epibatidineKapono,C.A. et al. (2013)
α3β4*S. scrofa>5uM0.5 nM [3H]epibatidineKapono,C.A. et al. (2013)
α4β2*R. norvegicus>10uM0.5 nM [3H]epibatidineKapono,C.A. et al. (2013)

Synthetic variants
MI [H5A]GRCCAPACGKNYSC(nh2)
MI [K10A]GRCCHPACGANYSC(nh2)
MI [N11A]GRCCHPACGKAYSC(nh2)
MI [P6A]GRCCHAACGKNYSC(nh2)
MI [R2A]GACCHPACGKNYSC(nh2)
MI [S13A]GRCCHPACGKNYAC(nh2)
MI [Y12A]GRCCHPACGKNASC(nh2)
MI [Y12Dit]GRCCHPACGKN(Dit)SC(nh2)
MI [Y12H]GRCCHPACGKNHSC(nh2)
MI [Y12M]GRCCHPACGKNMSC(nh2)
MI [Y12W]GRCCHPACGKNWSC(nh2)
MI [not amidated]GRCCHPACGKNYSC
MICCCHPACGKNYSC(nh2)
MI[del1G]RCCHPACGKNYSC(nh2)

References
McIntosh,M., Cruz,L.J., Hunkapiller,M.W., Gray,W.R. and Olivera,B.M. (1982) Isolation and structure of a peptide toxin from the marine snail Conus magus Arch. Biochem. Biophys. 218:329-334
Gray,W.R., Rivier,J.E., Galyean,R., Cruz,L.J. and Olivera,B.M. (1983) Conotoxin MI. Disulfide bonding and conformational states J. Biol. Chem. 258:12247-12251
Jacobsen,R.B., DelaCruz,R.G., Grose,J.H., McIntosh,J.M., Yoshikami,D. and Olivera,B.M. (1999) Critical residues influence the affinity and selectivity of alpha-conotoxin MI for nicotinic acetylcholine receptors Biochemistry 38:13310-13315
Johnson,D.S., Martinez,J., Elgoyhen,A.B., Heinemann,S.F. and McIntosh,J.M. (1995) alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors Mol. Pharmacol. 48:194-199
Kapono,C.A., Thapa,P., Cabalteja,C.C., Guendisch,D., Collier,A.C. and Bingham,J.P. (2013) Conotoxin truncation as a post-translational modification to increase the pharmacological diversity within the milked venom of Conus magus. Toxicon
Cortez,L., Marino-Buslje,C., de Jiménez Bonino,M.B. and Hellman,U. (2007) Interactions between alpha-conotoxin MI and the Torpedo marmorata receptor alpha-delta interface. Biochem. Biophys. Res. Commun. 355:275-279
Sine,S.M., Kreienkamp,H.J., Bren,N., Maeda,R. and Taylor,P. (1995) Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of determinants of alpha-conotoxin M1 selectivity. Neuron 15:205-211
Dudel,J. (2014) α-Conotoxin M1 (CTx) blocks αδ binding sites of adult nicotinic receptors while ACh binding at αε sites elicits only small and short quantal synaptic currents. Physiol Rep 2
Stock,P., Ljaschenko,D., Heckmann,M. and Dudel,J. (2014) Agonists binding nicotinic receptors elicit specific channel-opening patterns at αγ and αδ sites. J. Physiol. (Lond.) 592:2501-2517

Internal links
Nucleic acids
Structure

External links
UniProtKB/Swiss-Prot P01521
Ncbi P01521

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