CA1A_CONLM
ID CA1A_CONLM Reviewed; 17 AA.
AC P0DL68;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 1.
DT 25-MAY-2022, entry version 12.
DE RecName: Full=Alpha-conotoxin LsIA {ECO:0000303|PubMed:23924607};
OS Conus limpusi (Cone snail).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Eremiconus.
OX NCBI_TaxID=1967283;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP SYNTHESIS, AMIDATION AT CYS-17, MUTAGENESIS OF SER-1 AND 1-SER-GLY-2,
RP STRUCTURE BY NMR, AND DISULFIDE BOND.
RC TISSUE=Venom;
RX PubMed=23924607; DOI=10.1016/j.bcp.2013.07.016;
RA Inserra M.C., Kompella S.N., Vetter I., Brust A., Daly N.L., Cuny H.,
RA Craik D.J., Alewood P.F., Adams D.J., Lewis R.J.;
RT "Isolation and characterization of alpha-conotoxin LsIA with potent
RT activity at nicotinic acetylcholine receptors.";
RL Biochem. Pharmacol. 86:791-799(2013).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF SER-5 AND ASN-6.
RX PubMed=34753970; DOI=10.1038/s41598-021-01277-4;
RA Ho T.N.T., Abraham N., Lewis R.J.;
RT "Rigidity of loop 1 contributes to equipotency of globular and ribbon
RT isomers of alpha-conotoxin AusIA.";
RL Sci. Rep. 11:21928-21928(2021).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This globular toxin inhibits human alpha-7/CHRNA7 (IC(50)=0.3-10.1 nM),
CC rat alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=10.3 nM) and rat alpha-3-
CC alpha-5-beta-2/CHRNA3-CHRNB5-CHRNB2 (IC(50)=31.2 nM).
CC {ECO:0000269|PubMed:23924607, ECO:0000269|PubMed:34753970}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23924607}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:23924607}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- PTM: Amidation at Cys-17 plays a critical role, since a C-terminally
CC carboxylated analog is 3-fold less potent at the alpha-7/CHRNA7 nAChR
CC subtype and 3-fold more potent at the alpha-3-beta-2/CHRNA3-CHRNB2
CC subtype. {ECO:0000269|PubMed:23924607}.
CC -!- MASS SPECTROMETRY: Mass=1746.6; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:23924607};
CC -!- MISCELLANEOUS: Shows a weak inhibition of alpha-3-beta-4/CHRNA3-CHRNB4
CC nAChR and does not inhibit alpha-9-alpha-10/CHRNA9-CHRNA10, alpha-4-
CC beta-2/CHRNA4-CHRNB2 and alpha-4-beta-4/CHRNA4-CHRNB4 nAChR.
CC {ECO:0000269|PubMed:23924607}.
CC -!- MISCELLANEOUS: The synthetic ribbon toxin is much less potent that the
CC globular toxin (IC(50)=41 nM compared to 0.3 nM).
CC {ECO:0000269|PubMed:34753970}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0DL68; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR InterPro; IPR018072; Conotoxin_a-typ_CS.
DR Pfam; PF07365; Toxin_8; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Toxin.
FT PEPTIDE 1..17
FT /note="Alpha-conotoxin LsIA"
FT /evidence="ECO:0000269|PubMed:23924607"
FT /id="PRO_0000439831"
FT REGION 5..7
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 17
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:23924607"
FT DISULFID 3..9
FT /evidence="ECO:0000269|PubMed:23924607"
FT DISULFID 4..17
FT /evidence="ECO:0000269|PubMed:23924607"
FT MUTAGEN 1..2
FT /note="Missing: 9-fold and 4.4-fold decrease in ability to
FT inhibit alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7
FT nAChR subunits, respectively."
FT /evidence="ECO:0000269|PubMed:23924607"
FT MUTAGEN 1
FT /note="Missing: 5.5-fold and 2.3-fold decrease in potency
FT at alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7 nAChR
FT subunits, respectively."
FT /evidence="ECO:0000269|PubMed:23924607"
FT MUTAGEN 5
FT /note="S->AS: 160-fold decrease in ability to inhibit
FT alpha-7/CHRNA7 nAChR subunit."
FT /evidence="ECO:0000269|PubMed:34753970"
FT MUTAGEN 5
FT /note="S->R: No change in ability to inhibit alpha-7/CHRNA7
FT nAChR subunit."
FT /evidence="ECO:0000269|PubMed:34753970"
FT MUTAGEN 6
FT /note="N->RN: 26-fold decrease in ability to inhibit alpha-
FT 7/CHRNA7 nAChR subunit."
FT /evidence="ECO:0000269|PubMed:34753970"
SQ SEQUENCE 17 AA; 1752 MW; C339841BD4C98F0C CRC64;
SGCCSNPACR VNNPNIC
