MrIC (P06003) Protein Card

General Information
Name MrIC
Alternative name(s) Mr1.7[H13N],Mr1.7c,Mr1.8c
Organism Conus marmoreus
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Parent Mr1.7
Protein precursor Mr1.8 precursor (4571)
Notes This conotoxin is a co-agonist for nAChR. It is temporarily classified as an alpha-conotoxin but its classification should be changed (alpha-conotoxins are antagonists by definition).

Jin et al. 2014 stated that this peptide is coming from a precursor named Mr1.7 but the precursor they described was published under the name Mr1.8 by Liu et al 2012. Liu et al 2012 also published a peptide precursor Mr1.7 which is related but not identical to Mr1.8.

Mueller et al 2015 characterised the pharmacological activity and demonstrated that MrIC exclusively activates alpha-7 nAChR if modulated by type II allosteric modulators including PNU12059, TQS and SB-206553.

Wang et al. (2015) studied Mr1.7(H13N) which corresponds to MrIC.

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

Sequence
PECCTHPACHVSNPELC(nh2)
Modified residues
positionsymbolname
18nh2C-term amidation
Average Mass 1835.07
Monoisotopic Mass 1833.71
Isoelectric Point 5.63
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50Ref
α2β2R. norvegicus>10 uMWang et al. (2015)
α2β4R. norvegicus>10 uMWang et al. (2015)
α3β2R. norvegicus541.4 nM[395.1-7.42]Wang et al. (2015)
α3β4R. norvegicus>10 uMWang et al. (2015)
α4β2R. norvegicus>10 uMWang et al. (2015)
α4β4R. norvegicus>10 uMWang et al. (2015)
α7R. norvegicus2423 nM[1785-3289]Wang et al. (2015)
α9α10R. norvegicus1833 nM[1033-3250]Wang et al. (2015)

EC50: Nicotinic acetylcholine receptors

TargetOrganismEC50Ref
α7C. marmoreus(SB-206553 (150 uM))1.62 uMMueller,A. et al. (2015)
(Galantamine (10 uM))No responseMueller,A. et al. (2015)
(TQS (30 uM))47.8 uMMueller,A. et al. (2015)
(PNU120596 (25 uM))42.6 uMMueller,A. et al. (2015)
(PNU120596 (10 uM))1.9 uM+/-0.7Mueller,A. et al. (2015)
(PNU120596 (25 uM))63.1 uMMueller,A. et al. (2015)

References
Jin,A.H., Vetter,I., Dutertre,S., Abraham,N., Emidio,N.B., Inserra,M., Murali,S.S., Christie,M.J., Alewood,P.F. and Lewis,R.J. (2014) MrIC, a Novel α-Conotoxin Agonist in the Presence of PNU at Endogenous α7 Nicotinic Acetylcholine Receptors. Biochemistry 53:1-3
Mueller,A., Starobova,H., Inserra,M.C., Jin,A.H., Deuis,J.R., Dutertre,S., Lewis,R.J., Alewood,P.F., Daly,N.L. and Vetter,I. (2015) α-Conotoxin MrIC is a biased agonist at α7 nicotinic acetylcholine receptors. Biochem. Pharmacol. 94:155-163
Wang, S., Zhao, C., Liu, Z., Wang, X., Liu, N., Du, W. and Dai, Q. (2015) Structural and functional characterization of a novel α-conotoxin Mr1. 7 from Conus marmoreus targeting neuronal nAChR α3β2, α9α10 and α6/α3β2β3 subtypes Marine drugs 13:3259-3275
Gulsevin,A., Papke,R.L., Stokes,C., Tran,H.N.T., Jin,A.H., Vetter,I. and Meiler,J. (2021) The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site. Toxins (Basel) 13

Internal links
Protein Precursor Mr1.8 precursor (4571)
Nucleic acids
Structure

External links

Tools