MII [E11A] (P03892) Protein Card

General Information

Name	MII [E11A]
Organism	synthetic construct
Protein Type	Synthetic
Parent	MII
Notes	MII[E11A] has 500-5300-fold discrimination over MII for alpha6 subtypes in human and other primates (Turner et al. 2009). MII[E11A] may discriminate between two alpha6beta2 nAChR subtypes in rodent, primate & human striatum- very-high-affinity and high-affinity. These possibly represent alpha6alpha4beta2beta3 and alpha6beta2beta3 respectively(in mouse). Very-high-affinity alpha6beta2* population was primarily decreased with moderate negrostriatal lesions, high-affinity component was affected only with a more severe lesion. (Bordia et al. 2007)

Classification

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

Sequence

GCCSNPVCHLAHSNLC(nh2)

Modified residues

position	symbol	name
17	nh2	C-term amidation

Average Mass

1652.89

Monoisotopic Mass

1651.65

Isoelectric Point

8.42

Extinction Coefficient [280nm]

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism		IC50		n_hill	Agonist	Ref
α2β2	R. norvegicus		>10uM			100uM Ach	McIntosh,J.M. et al. (2004)
α2β4	R. norvegicus		>10uM			100uM Ach	McIntosh,J.M. et al. (2004)
α3β2	R. norvegicus		8.72nM			100uM Ach	McIntosh,J.M. et al. (2004)
			16.9nM	+/-2.9	0.7	70uM Ach	Everhart,D. et al. (2004)
α3β4	R. norvegicus		2.1uM			100uM Ach	McIntosh,J.M. et al. (2004)
α4β4	R. norvegicus		>10uM			100uM Ach	McIntosh,J.M. et al. (2004)
α6/α3β2	R. norvegicus		154pM			100uM Ach	McIntosh,J.M. et al. (2004)
α6/α3β2β3	R. norvegicus		160pM			100uM Ach	McIntosh,J.M. et al. (2004)
α6/α3β4	R. norvegicus		6.44nM			100uM Ach	McIntosh,J.M. et al. (2004)
α7	R. norvegicus		1.05uM			100uM Ach	McIntosh,J.M. et al. (2004)
a7α6β2	H. sapiens	(Autoradiography in striatum [caudate]. Very-high-affinity site.)	0.072pM	+/-0.026			Bordia,T. et al. (2007)
		(Autoradiography in striatum [caudate]. High-affinity site.)	35pM	+/-19			Bordia,T. et al. (2007)
		(Autoradiography in striatum [putamen]. Very-high-affinity site.)	0.078pM	+/-0.033			Bordia,T. et al. (2007)
		(Autoradiography in striatum [caudate]. High-affinity site.)	60pM	+/-19			Bordia,T. et al. (2007)
	M. musculus	(Autoradiography in striatum. Very-high-affinity site.)	0.029pM	+/-0.013			Bordia,T. et al. (2007)
		(Autoradiography in striatum. High-affinity site.)	17pM	+/-10			Bordia,T. et al. (2007)
	S. sciureus	(Autoradiography in striatum [dorsal putamen]. Very-high-affinity site.)	0.0049pM	+/-0.0015			Bordia,T. et al. (2007)
		(Autoradiography in striatum [dorsal putamen]. High-affinity site.)	33pM	+/-22			Bordia,T. et al. (2007)
		(Autoradiography in striatum [lateral caudate]. Very-high-affinity site.)	0.0083pM	+/-0.0021			Bordia,T. et al. (2007)
		(Autoradiography in striatum [lateral caudate]. High-affinity site.)	56pM	+/-34			Bordia,T. et al. (2007)
		(Autoradiography in striatum [ventral putamen]. High-affinity site.)	38pM	+/-27			Bordia,T. et al. (2007)
		(Autoradiography in striatum [ventral putamen]. Very-high-affinity site.)	0.0085pM	+/-0.0021			Bordia,T. et al. (2007)
		(Autoradiography in striatum [medial caudate]. High-affinity site.)	51pM	+/-32			Bordia,T. et al. (2007)
		(Autoradiography in striatum [medial caudate]. Very-high-affinity site.)	0.0097pM	+/-0.0028			Bordia,T. et al. (2007)

References

Everhart,D., Cartier,G.E., Malhotra,A., Gomes,A.V., McIntosh,J.M. and Luetje,C.W. (2004) Determinants of potency on alpha-conotoxin MII, a peptide antagonist of neuronal nicotinic receptors Biochemistry 43:2732-2737

Turner,M., Eidemiller,S., Martin,B., Narver,A., Marshall,J., Zemp,L., Cornell,K.A., McIntosh,J.M. and McDougal,O.M. (2009) Structural basis for alpha-conotoxin potency and selectivity. Bioorg. Med. Chem. 17:5894-5899

McIntosh,J.M., Azam,L., Staheli,S., Dowell,C., Lindstrom,J.M., Kuryatov,A., Garrett,J.E., Marks,M.J. and Whiteaker,P. (2004) Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors. Mol. Pharmacol. 65:944-952

Bordia,T., Grady,S.R., McIntosh,J.M. and Quik,M. (2007) Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse, monkey, and Parkinson Mol. Pharmacol. 72:52-61

Internal links

Nucleic acids
Structure	20 NMR solution structures of MII [E11A]

External links

Tools