Chemistry:BDS-1
| BDS-1 | |
|---|---|
| Identifiers | |
| Organism | Anemonia sulcata |
| Synonym | Kappa-actitoxin-Avd4a |
| PDB | 2BDS |
| Uniprot | P11494 |
Blood-depressing substance-1 (BDS-1), also known as kappa-actitoxin-Avd4a, is a polypeptide found in the venom of the snakelocks anemone Anemonia sulcata.[1] BDS-1 is a neurotoxin that modulates voltage-dependent potassium channels, in particular Kv3-family channels, as well as certain sodium channels.[2][3] This polypeptide belongs to the sea anemone type 3 toxin peptide family.[1]
Etymology
BDS-1 brings about a decrease in blood pressure by blocking Kv3 potassium channels. Thus, this protein is named after its antihypertensive function.[4]
Sources
BDS-1 is a toxin secreted by the nematocyst of Anemonia sulcata (Mediterranean snakelocks sea anemone).[1]
Chemistry
BDS-1 is a 43 amino acids long polypeptide chain, which consists of six cysteines linked by three disulfide bridges. The secondary structure of BDS-1 possesses three-stranded antiparallel β-sheets, along with one more short antiparallel β-sheet at its N-terminus.[5][6] When viewed along the polypeptide strand, its structure showa a right-handed twist.[6]
BDS-1 shares structural homology with the toxin BDS-2, which belongs to the same type-3 peptide family. It also displays around 24–26% identity with toxins AsI (ATX-I), AsII (ATX-II), and AsV (ATX-V) from Anemonia sulcata and AxI (AP-A) from Anthopleura xanthogrammica.[4]
Target
BDS-1 is an inhibitor of the fast inactivating Kv3-family channels, including Kv3.1, Kv3.2 and Kv3.4 channels.[2] Additionally, BDS-1 affects the inactivation of voltage-gated sodium channels, Nav1.1, Nav1.3, Nav1.6 and Nav1.7.[3]
Mode of action
BDS-1 modifies the voltage-dependent gating properties of Kv3 potassium channels by binding to the voltage sensitive domains on S3b and S4 subunits.[2] The toxin elicits a depolarizing shift in the conductance-voltage relation, making it more difficult to open, and slows both the activation and inactivation kinetics of these ion channels.[2]
In addition, BDS-1 enhances the current flowing through several voltage-gated sodium channels. The toxin binds to the S3-S4 linker of domain IV and slows the inactivation of the channel, resulting in increased current upon depolarization. BDS-1 has a very strong potency for the human Nav1.7 channel. In mice, BDS-1 slows the inactivation of Nav1.3 channels but has smaller effects on the inactivation of Nav1.1 and Nav1.6 channels. This is probably due to a different channel sensitivity for the toxin.[3]
Toxicity
By targeting Kv3.1a channels, BDS-1 concentrations at or above 3 μM are toxic to mouse fibroblasts.[2]
References
- ↑ 1.0 1.1 1.2 "UniProtKB - P11494 (BDS1_ANESU)". https://www.uniprot.org/uniprot/P11494.
- ↑ 2.0 2.1 2.2 2.3 2.4 Yeung, Shuk Yin M. (2005). "Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies". Journal of Neuroscience 25 (38): 8735–45. doi:10.1523/JNEUROSCI.2119-05.2005. PMID 16177043.
- ↑ 3.0 3.1 3.2 Liu, Pin; Sooyeon Jo; Bruce P. Bean (2012). "Modulation of neuronal sodium channels by the sea anemone peptide BDS-I". Journal of Neurophysiology 107 (11): 3155–67. doi:10.1152/jn.00785.2011. PMID 22442564.
- ↑ 4.0 4.1 Diochot, Sylvie (1998). "Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3. 4". Journal of Biological Chemistry 273 (12): 6744–9. doi:10.1074/jbc.273.12.6744. PMID 9506974.
- ↑ Frazão, Bárbara; Vitor Vasconcelos; Agostinho Antunes (2012). "Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: an overview". Marine Drugs 10 (12): 1812–51. doi:10.3390/md10081812. PMID 23015776.
- ↑ 6.0 6.1 Driscoll, Paul C. (1989). "A proton nuclear magnetic resonance study of the antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia sulcata: sequential and stereospecific resonance assignment and secondary structure". Biochemistry 28 (5): 2178–87. doi:10.1021/bi00431a032. PMID 2566325.
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