CA1A_CONAV
ID CA1A_CONAV Reviewed; 16 AA.
AC P0DL39;
DT 04-FEB-2015, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Alpha-conotoxin AusIA {ECO:0000303|PubMed:25194747, ECO:0000303|PubMed:34753970};
OS Conus australis (Austral cone) (Asprella australis).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Phasmoconus.
OX NCBI_TaxID=1519798;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom duct;
RX PubMed=25194747; DOI=10.1016/j.toxicon.2014.08.074;
RA Lebbe E.K., Peigneur S., Maiti M., Mille B.G., Devi P., Ravichandran S.,
RA Lescrinier E., Waelkens E., D'Souza L., Herdewijn P., Tytgat J.;
RT "Discovery of a new subclass of alpha-conotoxins in the venom of Conus
RT australis.";
RL Toxicon 91:145-154(2014).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.46 ANGSTROMS) OF RIBBON AND GLOBULAR TOXINS IN
RP COMPLEX WITH L.STAGNALIS ACETYLCHOLINE-BINDING PROTEIN, 3D-STRUCTURE
RP MODELING IN COMPLEX WITH ALPHA-7/CHRNA7 NACHR, SYNTHESIS, AND MUTAGENESIS
RP OF SER-1; ALA-4; ARG-5; ASN-6; PRO-7; ARG-10 AND HIS-11.
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 peptide has been experimentally synthesized as AusIA-globular and
CC AusIA-ribbon. Both forms are active on chicken alpha-7/CHRNA7 nAChR
CC with similar potency (micromolar range). {ECO:0000269|PubMed:25194747,
CC ECO:0000269|PubMed:34753970}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25194747}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:25194747}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha5/5 pattern.
CC {ECO:0000305}.
CC -!- DOMAIN: The equipotent ability to inhibit alpha-7/CHRNA7 nAChR subunit
CC by both the globular and ribbon toxin arise mainly from the insertion
CC of an additional residue in the first loop and partly from residues in
CC the termini. {ECO:0000269|PubMed:34753970}.
CC -!- PTM: Two isomers (with different disulfide connectivity) have been
CC synthesized (AusIA-globular (C1-C3, C2-C4) and AusIA-ribbon (C1-C4, C2-
CC C3)). Only AusIA-globular contains the cysteine connectivity described
CC as typical for native alpha-conotoxins. However, AusIA-ribbon is more
CC potent than AusIA-globular, suggesting that another disulfide
CC connectivity may exist in nature. Both isomers adopt very flexible
CC structures without having a unique folded structure, lacking any stable
CC alpha-helical and/or beta-turn units. {ECO:0000303|PubMed:25194747}.
CC -!- MASS SPECTROMETRY: Mass=1763.90; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:25194747};
CC -!- MISCELLANEOUS: Neither AusIA-globular nor AusIA-ribbon shows effect on
CC muscle nAChRs alpha-1-beta-1-epsilon-delta/CHRNA1-CHRNB1-CHRNE-CHRND
CC (adult subtype) and alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-
CC CHRND (fetal subtype) and on neuronal nAChRs alpha-3-beta-4/CHRNA3-
CC CHRNB4, alpha-4-beta-4/CHRNA4-CHRNB4 and alpha-4-beta-2/CHRNA4-CHRNB2.
CC {ECO:0000269|PubMed:25194747}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR PDB; 7N0W; X-ray; 2.46 A; G=1-16.
DR PDB; 7N0Y; X-ray; 2.58 A; G=1-16.
DR PDBsum; 7N0W; -.
DR PDBsum; 7N0Y; -.
DR AlphaFoldDB; P0DL39; -.
DR SMR; P0DL39; -.
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.
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..16
FT /note="Alpha-conotoxin AusIA"
FT /evidence="ECO:0000269|PubMed:25194747"
FT /id="PRO_0000431736"
FT SITE 4
FT /note="Important for the structural rigidity of the
FT globular toxin, which impacts ability to inhibit alpha-
FT 7/CHRNA7 nAChR"
FT SITE 5
FT /note="Important for the structural rigidity of the
FT globular toxin, which impacts ability to inhibit alpha-
FT 7/CHRNA7 nAChR"
FT DISULFID 2..15
FT /note="In AusIA-ribbon form; alternate"
FT /evidence="ECO:0000269|PubMed:34753970,
FT ECO:0000305|PubMed:25194747, ECO:0007744|PDB:7N0W"
FT DISULFID 2..9
FT /note="In AusIA-globular form; alternate"
FT /evidence="ECO:0000269|PubMed:34753970,
FT ECO:0007744|PDB:7N0Y"
FT DISULFID 3..15
FT /note="In AusIA-globular form; alternate"
FT /evidence="ECO:0000269|PubMed:34753970,
FT ECO:0007744|PDB:7N0Y"
FT DISULFID 3..9
FT /note="In AusIA-ribbon form; alternate"
FT /evidence="ECO:0000269|PubMed:34753970,
FT ECO:0000305|PubMed:25194747, ECO:0007744|PDB:7N0W"
FT MUTAGEN 1
FT /note="S->G: No change in ability to inhibit alpha-7/CHRNA7
FT nAChR for globular toxin. 2-fold decrease in ability to
FT inhibit alpha-7/CHRNA7 nAChR for ribbon toxin."
FT MUTAGEN 4
FT /note="A->S: 1.5-fold decrease in ability to inhibit alpha-
FT 7/CHRNA7 nAChR for globular toxin. 2.65-fold decrease in
FT ability to inhibit alpha-7/CHRNA7 nAChR for ribbon toxin."
FT MUTAGEN 4
FT /note="Missing: 47-fold increase in ability to inhibit
FT alpha-7/CHRNA7 nAChR for globular toxin. 2.3-fold increase
FT in ability to inhibit alpha-7/CHRNA7 nAChR for ribbon
FT toxin."
FT MUTAGEN 5
FT /note="R->A: Loss of ability to inhibit alpha-7/CHRNA7
FT nAChR for both globular and ribbon toxins."
FT MUTAGEN 5
FT /note="R->S: Loss of ability to inhibit alpha-7/CHRNA7
FT nAChR for globular toxin. 2.7-fold decrease in ability to
FT inhibit alpha-7/CHRNA7 nAChR for ribbon toxin."
FT MUTAGEN 5
FT /note="Missing: 80-fold increase in ability to inhibit
FT alpha-7/CHRNA7 nAChR for globular toxin. Loss of ability to
FT inhibit alpha-7/CHRNA7 nAChR for ribbon toxin."
FT MUTAGEN 7
FT /note="P->A: Loss of ability to inhibit alpha-7/CHRNA7
FT nAChR for both globular and ribbon toxins."
FT MUTAGEN 10
FT /note="R->A: Loss of ability to inhibit alpha-7/CHRNA7
FT nAChR for both globular and ribbon toxins."
FT MUTAGEN 11
FT /note="H->L: Loss of ability to inhibit alpha-7/CHRNA7
FT nAChR for globular toxin. No change in ability to inhibit
FT alpha-7/CHRNA7 nAChR for ribbon toxin."
FT MUTAGEN 16
FT /note="Missing: 4-fold increase in ability to inhibit
FT alpha-7/CHRNA7 nAChR for globular toxin. 2.3-fold decrease
FT in ability to inhibit alpha-7/CHRNA7 nAChR for ribbon
FT toxin."
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:7N0Y"
FT HELIX 7..12
FT /evidence="ECO:0007829|PDB:7N0Y"
SQ SEQUENCE 16 AA; 1768 MW; 2B1EEBD02E1629C7 CRC64;
SCCARNPACR HNHPCV
