ID   CA1A_CONLG              Reviewed;          18 AA.
AC   X1WB75;
DT   03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 1.
DT   25-MAY-2022, entry version 25.
DE   RecName: Full=Alpha-conotoxin Lo1a {ECO:0000303|PubMed:24567324};
OS   Conasprella longurionis (Cone snail) (Conus longurionis).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conasprella; Fusiconus.
OX   NCBI_TaxID=1077918;
RN   [1]
RP   PROTEIN SEQUENCE, SYNTHESIS, MASS SPECTROMETRY, MUTAGENESIS OF ASP-18,
RP   STRUCTURE BY NMR, FUNCTION, DISULFIDE BOND, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=24567324; DOI=10.1074/jbc.m114.556175;
RA   Lebbe E.K., Peigneur S., Maiti M., Devi P., Ravichandran S., Lescrinier E.,
RA   Ulens C., Waelkens E., D'Souza L., Herdewijn P., Tytgat J.;
RT   "Structure-function elucidation of a new alpha-conotoxin, Lo1a, from Conus
RT   longurionis.";
RL   J. Biol. Chem. 289:9573-9583(2014).
CC   -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC       the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC       This peptide is active on neuronal nAChRs alpha-7/CHRNA7 (IC(50) of
CC       3.24 uM), alpha-3-beta-4/CHRNA3-CHRNB4, alpha-4-beta-2/CHRNA4-CHRNB2,
CC       and alpha-4-beta-4/CHRNA4-CHRNB4. 10 uM of this peptide inhibits these
CC       receptors by 85%, 40%, 19%, and 13%, respectively.
CC       {ECO:0000269|PubMed:24567324}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24567324}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:24567324}.
CC   -!- DOMAIN: The cysteine framework is I (CC-C-C). {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=1930.12; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:24567324};
CC   -!- MISCELLANEOUS: Does not show effect on the muscle nAChRs alpha-1-beta-
CC       1-epsilon-delta/CHRNA1-CHRNB1-CHRNE-CHRND (adult subtype) and alpha-1-
CC       beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND (fetal subtype).
CC       {ECO:0000305|PubMed:24567324}.
CC   -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR   PDB; 2MD6; NMR; -; A=1-18.
DR   PDBsum; 2MD6; -.
DR   AlphaFoldDB; X1WB75; -.
DR   BMRB; X1WB75; -.
DR   SMR; X1WB75; -.
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:0099106; F:ion channel regulator 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.
DR   PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylcholine receptor inhibiting toxin;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT   PEPTIDE         1..18
FT                   /note="Alpha-conotoxin Lo1a"
FT                   /evidence="ECO:0000269|PubMed:24567324"
FT                   /id="PRO_0000430171"
FT   DISULFID        3..9
FT                   /evidence="ECO:0000269|PubMed:24567324"
FT   DISULFID        4..17
FT                   /evidence="ECO:0000269|PubMed:24567324"
FT   MUTAGEN         18
FT                   /note="D->RRR: Is more potent at the alpha-7 nAChR
FT                   (IC(50)=1.06 uM), and surprinsingly inhibits the adult
FT                   muscle subtype alpha-1/beta-1/delta/epsilon (IC(50)=1.47 uM
FT                   or 82% when 10 uM of the peptide are tested), but not the
FT                   fetal subtype alpha-1/beta-1/delta/gamma."
FT                   /evidence="ECO:0000269|PubMed:24567324"
FT   MUTAGEN         18
FT                   /note="Missing: Is more potent at the alpha-7 nAChR
FT                   (IC(50)=0.80 nM), and surprinsingly inhibits the adult
FT                   muscle subtype alpha-1/beta-1/delta/epsilon (IC(50)=4.40 uM
FT                   or 80% when 10 uM of the peptide are tested), and the fetal
FT                   muscle subtype alpha-1/beta-1/delta/gamma (38% when 10 uM
FT                   of the peptide are tested)."
FT                   /evidence="ECO:0000269|PubMed:24567324"
FT   STRAND          3..6
FT                   /evidence="ECO:0007829|PDB:2MD6"
FT   HELIX           7..10
FT                   /evidence="ECO:0007829|PDB:2MD6"
FT   HELIX           14..16
FT                   /evidence="ECO:0007829|PDB:2MD6"
SQ   SEQUENCE   18 AA;  1935 MW;  3B5A473B4BD1698C CRC64;
     EGCCSNPACR TNHPEVCD