We report the purifi
cation and
chara
cterization of a new
conotoxin from the venom of
Conusradiatus. The peptide,
![](/images/gif<font color=)
chars/alpha.gif" BORDER=0>S-
conotoxin RVIIIA (
![](/images/gif<font color=)
chars/alpha.gif" BORDER=0>S-RVIIIA), is bio
chemi
cally unique with respe
ct to itsamino a
cid sequen
ce, post-translational modifi
cation, and mole
cular targets. In
comparison to other ni
cotini
cantagonists from
Conus venoms,
![](/images/gif<font color=)
chars/alpha.gif" BORDER=0>S-RVIIIA exhibits an unusually broad targeting spe
cifi
city for ni
cotini
ca
cetyl
choline re
ceptor (nAChR) subtypes, as assayed by ele
ctrophysiology. The toxin is paralyti
c to mi
ceand fish,
consistent with its nearly irreversible blo
ck of the neuromus
cular nAChR. Similar to otherantagonists of
certain neuronal nAChRs, the toxin also eli
cits seizures in mi
ce upon intra
cranial inje
ction.The only previously
chara
cterized
conotoxin from the S superfamily,
![](/images/gif<font color=)
chars/sigma.gif" BORDER=0 >-
conotoxin GVIIIA, is a spe
cifi
ccompetitive antagonist of the 5-HT
3 re
ceptor; thus,
![](/images/gif<font color=)
chars/alpha.gif" BORDER=0>S-RVIIIA defines a novel family of ni
cotini
cantagonists within the S superfamily. All previously
chara
cterized
competitive
conotoxin nAChR antagonistshave been members of the A superfamily of
conotoxins. Our working hypothesis is that the parti
culargroup of fish-hunting
Conus spe
cies that in
cludes
Conus radiatus uses the
![](/images/gif<font color=)
chars/alpha.gif" BORDER=0>S-
conotoxin family to targetthe mus
cle nAChR and paralyze prey.