TPDB

3D PDB MODEL

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TPDB ID TPDB72671

Activity

Neurotoxin

Activity_category_statistics

Toxicity and safety peptides

Database_Source

NTxPred2

Sequence_Type

standard

Has_Modification No

Description A 123-aa standard natural neurotoxin peptide sequence curated from NTxPred2, with an available 3D structural model.

Sequence

MAMNMSMTLCMFVMVVVAATVIDSTQLQEPDLSRMRRSGPADCCRMKECCTDRVNECLQRYSGREDKFVSFCYQEATVTCGSFNEIVGCCYGYQMCMIRVVKPNSLSGAHEACKTVSCGNPCA

FASTA

>TPDB72671|Neurotoxin|length=123
MAMNMSMTLCMFVMVVVAATVIDSTQLQEPDLSRMRRSGPADCCRMKECCTDRVNECLQRYSGREDKFVSFCYQEATVTCGSFNEIVGCCYGYQMCMIRVVKPNSLSGAHEACKTVSCGNPCA

Formula C566H913N163O179S24

Absent Amino Acids W

Common Amino Acids C

Mass 13634.90

PI 6.58

Basic Residues 13

Acidic Residues 12

Hydrophobic Residues 46

Net Charge -1

Boman Index 22.65

Hydrophobicity 0.028

Aliphatic Index 60.16

Half Life

Mammalian: 30 hour Yeast: >20 hour E.coli: >10 hour

Extinction Coefficient Cystines 6835

Absorbance 280nm 50.13

Polar Residues 45

number

8

A

8

R

5

N

5

D

14

C

7

E

5

Q

7

G

1

H

3

I

5

L

4

K

10

M

4

F

4

P

10

S

7

T

0

W

4

Y

12

V

Amino Acid Distribution

A: 8 R: 8 N: 5 D: 5 C: 14 E: 7 Q: 5 G: 7 H: 1 I: 3 L: 5 K: 4 M: 10 F: 4 P: 4 S: 10 T: 7 W: 0 Y: 4 V: 12

Length

123

Formula

C566H913N163O179S24

Mass

13634.90

PI

6.58

Net Charge

-1

Boman Index

22.65

Hydrophobicity

0.028

Evidence 1 Activity

Activity

Detail Source Activity Neurotoxin

Function Text

FUNCTION: Potently and selectively blocks the desensitization of ionotropic glutamate AMPA receptors (GRIA1, GRIA2, GRIA3 and GRIA4) (PubMed:19481459, PubMed:35377397). Binds to a different site than does the drug cyclothiazide (PubMed:19481459). The toxin acts like a straitjacket on the 'gating ring' of the ligand-binding domain (LBD) of the receptor (PubMed:25103405). It does so by restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD 'clamshells' is transduced into an irislike expansion of the gating ring (PubMed:25103405). Compared to other desensitization blockers, it is a poor stabilizer of the open channel because toxin-bound AMPA receptors undergo frequent brief closures (PubMed:35377397). In vitro, application of the toxin to hippocampal slices causes a large and rapid increase in resting AMPA receptor-mediated current leading to neuronal death (PubMed:19481459). {ECO:0000269|PubMed:19481459, ECO:0000269|PubMed:25103405}.

Target

Target or Channel glutamate receptor

Source & Reference

Database Source NA

Source UniProtKB/Swiss-Prot Tox-Prot

Other

Organism Source Conus striatus (Striated cone)

Neurotoxin Type Neurotoxin Postsynaptic neurotoxin Ion channel impairing toxin Ionotropic glutamate receptor inhibitor

Mechanism

Potently and selectively blocks the desensitization of ionotropic glutamate AMPA receptors (GRIA1, GRIA2, GRIA3 and GRIA4) (PubMed:19481459, PubMed:35377397). Binds to a different site than does the drug cyclothiazide (PubMed:19481459).

Protein Name Con-ikot-ikot (CII)

Venom Taxon Group cone snail

Protein Existence Evidence at protein level

Keywords 3D-structure Direct protein sequencing Disulfide bond Ion channel impairing toxin Ionotropic glutamate receptor inhibitor Neurotoxin Postsynaptic neurotoxin Secreted Signal Toxin

Tissue Specificity TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.

Keywords

3D-structure Direct protein sequencing Disulfide bond Ion channel impairing toxin Ionotropic glutamate receptor inhibitor Neurotoxin Postsynaptic neurotoxin Secreted Signal Toxin

Neurotoxin_Type

Neurotoxin Postsynaptic neurotoxin Ion channel impairing toxin Ionotropic glutamate receptor inhibitor

Protein_Existence

Evidence at protein level

Protein_Name

Con-ikot-ikot (CII)

Tissue_Specificity

TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.

Venom_Taxon_Group

cone snail